TY  - THES
AU  - Vučićević, Jelica
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7680
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:22869/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048438370
UR  - https://nardus.mpn.gov.rs/handle/123456789/17590
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3723
AB  - Ligandi imidazolinskih receptora predstavljaju veliku grupu biološki aktivnih jedinjenja koja svoju aktivnost ostvaruju delovanjem na imidazolinske receptore (I1-IR, I2-IR, and I3-IR) i na α2-adrenergičke receptore (α2-AR). Centralni antihipertenzivni efekat imidazolina kao što su klonidin, rilmenidin i moksonidin je rezultat aktivacije I1-IR and α2-AR. I2-imidazolinski receptori predstavljaju katalitičko mesto monoamino oksidaze B (MAO-B), enzima koji je uključen u nekolio neuroloških poremećaja. Jedinjenja kao što su idazoksan i njegovi analozi pokazuju visok afinitet za ovaj tip receptora. I3-IRs imaju ulogu u indukciju sekrecije insulina iz β-ćelija pankreasa i održavanje homeostaze glukoze. Imajući u vidu da većina liganada imidazolinskih receptora svoje efekate ostvaruje unutar centralnog nervnog sistema (CNS) delujući kao centralni antihipertenzivi i/ili su potencijalni lekovi u lečenju neuroloških oboljenja, procena njihove permeabilnosti kroz krvno-moždanu barijeru (KMB) je od suštinskog značaja u ranom otkriću lekova.U ovoj disertaciji KMB permeabilnost 18 liganda α2-adrenergičkih i/ili imidazolinskih receptora i 22 leka koja deluju na CNS je ispitana primenom paralelnog testa permeabilnosti na veštačkim membrana (eng. Parallel Artificial Membrane Permeability Assay, PAMPA) i bioparticione micelarne hromatografije (eng. Biopartitioning Micellar Chromatography, BMC). Vrednosti dobijene PAMPA (logPe) i BMC (logkBMC) su dalje analizirane kvantitativnim odnosom strukture i permeabilnosti jedinjenja (eng. Quantitative Structure-Permeability Relationship, QSPR).Dominantni molekulski/kajonski oblici na pH = 7,4 su određeni korišćenjem MarvinSketch 6.1.0 softvera. Geometrija odabranih molekulskih/katjonskih oblika ispitivanih jedinjenja je optimizovana primenom B3LYP /6-31G (d,p) nivoa Density Functional Theory (DTF) u ChemBio3D Ultra 13.0 programu. Deskriptori optimizovanih struktura su izračunati u ChemBio3D Ultra 13.0, Dragon 6.0 i ADMET Predictor 6.5 programima. logPe i logkBMC vrednosti su korišćene kao zavisne varijable (Y), dok suizračunati molekulski parametri predstavljali nezavisne varijable (X) u QSPR studiji.
AB  - Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both α2-adrenoreceptors (α2-AR) and imidazoline receptors (I1-IR, I2-IR, and I3-IR). The central hypotensive effect of imidazoline derivatives such as clonidine, rilmenidine and moxonidine is results of activation both I1-IR and α2-AR. I2-IRs have been shown to be modulatory site for monoamine oxidase-B, enzyme responsible for several neurological disorders. This type of imidazoline ligand receptors have high affinity for idazoxan and its analogues. I3-IRs are involved in induction of insulin secretion from β-cells and maintaining glucose homeostasis. Since the most IRs ligands are examined as centrally acting antihypertensives and/or drug candidates for treatment of various neurological diseases, predicting their brain penetration is a critical step in early drug discovery phase.In the framework of this doctoral dissertation, the effective Blood–Brain Barrier (BBB) permeability of 18 IRs/ α2-AR ligands and 22 Central Nervous System (CNS) drugs was experimentally determined by using both Parallel Artificial Membrane Permeability Assay (PAMPA) and Biopartitioning Micellar Chromatography (BMC) and further studied by the Quantitative-Structure-Permeability Relationship (QSPR) methodology.The dominant molecules/cations species of compounds have been calculated at pH = 7.4 by using MarvinSketch 6.1.0 software. The analyzed ligands were optimized using Density Functional Theory (B3LYP/6-31G(d,p)) included in ChemBio3D Ultra 13.0 program and molecule descriptors for optimized compounds were calculated using ChemBio3D Ultra 13.0, Dragon 6.0 and ADMET predictor 6.5 software. PAMPA effective permeabilities of examined compounds (logPe) and their logkBMC values were used as dependent variable (Y), while calculated molecular parametres were used as independent variables (X) in the QSPR study. SIMCA P+ 12.0 was used for Partial Least Square (PLS) analysis, while the stepwise Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) modeling were performed using STASTICA Neural Networks 4.0. Predictive potential of the formed models was confirmed by Leave-One-Out Cross- and external-validation and the most reliable models were selected.The descriptors that are important for model building are identified as well as their influence on BBB permeability...
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Heminformatička analiza, dizajn i ispitivanje proapoptotske aktivnosti novih liganada imidazolinskih receptora
UR  - https://hdl.handle.net/21.15107/rcub_nardus_17590
ER  - 

@phdthesis{
author = "Vučićević, Jelica",
year = "2020",
abstract = "Ligandi imidazolinskih receptora predstavljaju veliku grupu biološki aktivnih jedinjenja koja svoju aktivnost ostvaruju delovanjem na imidazolinske receptore (I1-IR, I2-IR, and I3-IR) i na α2-adrenergičke receptore (α2-AR). Centralni antihipertenzivni efekat imidazolina kao što su klonidin, rilmenidin i moksonidin je rezultat aktivacije I1-IR and α2-AR. I2-imidazolinski receptori predstavljaju katalitičko mesto monoamino oksidaze B (MAO-B), enzima koji je uključen u nekolio neuroloških poremećaja. Jedinjenja kao što su idazoksan i njegovi analozi pokazuju visok afinitet za ovaj tip receptora. I3-IRs imaju ulogu u indukciju sekrecije insulina iz β-ćelija pankreasa i održavanje homeostaze glukoze. Imajući u vidu da većina liganada imidazolinskih receptora svoje efekate ostvaruje unutar centralnog nervnog sistema (CNS) delujući kao centralni antihipertenzivi i/ili su potencijalni lekovi u lečenju neuroloških oboljenja, procena njihove permeabilnosti kroz krvno-moždanu barijeru (KMB) je od suštinskog značaja u ranom otkriću lekova.U ovoj disertaciji KMB permeabilnost 18 liganda α2-adrenergičkih i/ili imidazolinskih receptora i 22 leka koja deluju na CNS je ispitana primenom paralelnog testa permeabilnosti na veštačkim membrana (eng. Parallel Artificial Membrane Permeability Assay, PAMPA) i bioparticione micelarne hromatografije (eng. Biopartitioning Micellar Chromatography, BMC). Vrednosti dobijene PAMPA (logPe) i BMC (logkBMC) su dalje analizirane kvantitativnim odnosom strukture i permeabilnosti jedinjenja (eng. Quantitative Structure-Permeability Relationship, QSPR).Dominantni molekulski/kajonski oblici na pH = 7,4 su određeni korišćenjem MarvinSketch 6.1.0 softvera. Geometrija odabranih molekulskih/katjonskih oblika ispitivanih jedinjenja je optimizovana primenom B3LYP /6-31G (d,p) nivoa Density Functional Theory (DTF) u ChemBio3D Ultra 13.0 programu. Deskriptori optimizovanih struktura su izračunati u ChemBio3D Ultra 13.0, Dragon 6.0 i ADMET Predictor 6.5 programima. logPe i logkBMC vrednosti su korišćene kao zavisne varijable (Y), dok suizračunati molekulski parametri predstavljali nezavisne varijable (X) u QSPR studiji., Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both α2-adrenoreceptors (α2-AR) and imidazoline receptors (I1-IR, I2-IR, and I3-IR). The central hypotensive effect of imidazoline derivatives such as clonidine, rilmenidine and moxonidine is results of activation both I1-IR and α2-AR. I2-IRs have been shown to be modulatory site for monoamine oxidase-B, enzyme responsible for several neurological disorders. This type of imidazoline ligand receptors have high affinity for idazoxan and its analogues. I3-IRs are involved in induction of insulin secretion from β-cells and maintaining glucose homeostasis. Since the most IRs ligands are examined as centrally acting antihypertensives and/or drug candidates for treatment of various neurological diseases, predicting their brain penetration is a critical step in early drug discovery phase.In the framework of this doctoral dissertation, the effective Blood–Brain Barrier (BBB) permeability of 18 IRs/ α2-AR ligands and 22 Central Nervous System (CNS) drugs was experimentally determined by using both Parallel Artificial Membrane Permeability Assay (PAMPA) and Biopartitioning Micellar Chromatography (BMC) and further studied by the Quantitative-Structure-Permeability Relationship (QSPR) methodology.The dominant molecules/cations species of compounds have been calculated at pH = 7.4 by using MarvinSketch 6.1.0 software. The analyzed ligands were optimized using Density Functional Theory (B3LYP/6-31G(d,p)) included in ChemBio3D Ultra 13.0 program and molecule descriptors for optimized compounds were calculated using ChemBio3D Ultra 13.0, Dragon 6.0 and ADMET predictor 6.5 software. PAMPA effective permeabilities of examined compounds (logPe) and their logkBMC values were used as dependent variable (Y), while calculated molecular parametres were used as independent variables (X) in the QSPR study. SIMCA P+ 12.0 was used for Partial Least Square (PLS) analysis, while the stepwise Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) modeling were performed using STASTICA Neural Networks 4.0. Predictive potential of the formed models was confirmed by Leave-One-Out Cross- and external-validation and the most reliable models were selected.The descriptors that are important for model building are identified as well as their influence on BBB permeability...",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Heminformatička analiza, dizajn i ispitivanje proapoptotske aktivnosti novih liganada imidazolinskih receptora",
url = "https://hdl.handle.net/21.15107/rcub_nardus_17590"
}

Vučićević, J.. (2020). Heminformatička analiza, dizajn i ispitivanje proapoptotske aktivnosti novih liganada imidazolinskih receptora. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_17590

Vučićević J. Heminformatička analiza, dizajn i ispitivanje proapoptotske aktivnosti novih liganada imidazolinskih receptora. in Универзитет у Београду. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_17590 .

Vučićević, Jelica, "Heminformatička analiza, dizajn i ispitivanje proapoptotske aktivnosti novih liganada imidazolinskih receptora" in Универзитет у Београду (2020),
https://hdl.handle.net/21.15107/rcub_nardus_17590 .

TY  - JOUR
AU  - Đikić, Teodora
AU  - Vučićević, Jelica
AU  - Laurila, Jonne
AU  - Radi, Marco
AU  - Veljković, Nevena
AU  - Xhaard, Henri
AU  - Nikolić, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3639
AB  - Based on the finding that a central antihypertensive agent with high affinity for I1-type imidazoline receptors – rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α-adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α-adrenoceptors belong to the rhodopsin-like class A of G-protein-coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class. Therefore, to investigate possible off-target effects of imidazoline ligands we have prepared a reverse docking protocol on class A GPCRs, using imidazoline ligands and their decoys. To verify our in silico results, three ligands with high scores and three ligands with low scores were tested for antagonistic activity on α2- adrenoceptors.
PB  - Wiley-VCH Verlag
T2  - Molecular Informatics
T1  - Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field
VL  - 39
IS  - 7
DO  - 10.1002/minf.201900165
ER  - 

@article{
author = "Đikić, Teodora and Vučićević, Jelica and Laurila, Jonne and Radi, Marco and Veljković, Nevena and Xhaard, Henri and Nikolić, Katarina",
year = "2020",
abstract = "Based on the finding that a central antihypertensive agent with high affinity for I1-type imidazoline receptors – rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α-adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α-adrenoceptors belong to the rhodopsin-like class A of G-protein-coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class. Therefore, to investigate possible off-target effects of imidazoline ligands we have prepared a reverse docking protocol on class A GPCRs, using imidazoline ligands and their decoys. To verify our in silico results, three ligands with high scores and three ligands with low scores were tested for antagonistic activity on α2- adrenoceptors.",
publisher = "Wiley-VCH Verlag",
journal = "Molecular Informatics",
title = "Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field",
volume = "39",
number = "7",
doi = "10.1002/minf.201900165"
}

Đikić, T., Vučićević, J., Laurila, J., Radi, M., Veljković, N., Xhaard, H.,& Nikolić, K.. (2020). Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field. in Molecular Informatics
Wiley-VCH Verlag., 39(7).
https://doi.org/10.1002/minf.201900165

Đikić T, Vučićević J, Laurila J, Radi M, Veljković N, Xhaard H, Nikolić K. Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field. in Molecular Informatics. 2020;39(7).
doi:10.1002/minf.201900165 .

Đikić, Teodora, Vučićević, Jelica, Laurila, Jonne, Radi, Marco, Veljković, Nevena, Xhaard, Henri, Nikolić, Katarina, "Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field" in Molecular Informatics, 39, no. 7 (2020),
https://doi.org/10.1002/minf.201900165 . .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Oluić, Jelena
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Gagić, Žarko
AU  - Filipić, Slavica
AU  - Agbaba, Danica
AU  - Čudina, Olivera
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5473
AB  - Multi-target compounds are designed to act on at least two targets in synergistic way, in order to produce stronger biological effect. The link
between cancer and inflammation has been intensively studied in last years and inhibition of both COX-2 and 5-LOX enzymes may be an
effective therapeutic approach for colon cancer treatment [1]. Acridines are known as DNA-topoisomerase II inhibitors. These compounds
intercalate into the DNA and inhibit topoisomerase II by their side chain. Recent studies showed additional activities of acridine derivatives,
depending on the side chain structure, such as inhibition of Src, MEK and VEGFR2 kinases [2,3]. Altered activity of PI3K/mTOR signaling pathway
is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably
attractive concept in potential cancer treatment [4]. In this paper, design of three groups of multi-target compounds with potential anticancer
activity is presented. Designed compounds are potential inhibitors of COX-2 and 5-LOX, DNA-topoisomerase II complex and kinases (Src, MEK
and VEGFR2), as well as dual inhibitors of mTOR and PI3K. A set of 27 compounds with published inhibitory activity on COX-2 and 5-LOX was
formed and two QSAR models, for both activities, were created in Pentacle program. On the basis of models’ interpretation, nine new
compounds were designed and activity on both targets predicted by developed models. Twenty-three acridine derivatives were designed and
their interactions with DNA-topoisomerase II complex, Src, MEK and VEGFR2 were tested using AutoDock Vina program. Nineteen designed
compounds bind to DNA similarly to inhibitor amsacrine and among them, ten derivatives show key binding interactions with tested kinases and
therefore possess potential to inhibit them. A dataset of eighty-five compounds with dual PI3K/mTOR inhibitory activities was formed,
divided into two groups based on their structural analogy and 3D-QSAR analysis of each group was performed in Pentacle program,
9
resulting in four QSAR models. On the basis of these results, new compounds were designed and further evaluated by use of molecular
docking, virtual screening and ADMET predictions. Finally, seven compounds were chosen as the most promising new dual mTOR/PI3K inhibitors.
PB  - COST Action 17104 (STRATAGEM)
C3  - STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy
T1  - Rational design of multi-target compounds with potential anticancer activity
SP  - 8
EP  - 9
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5473
ER  - 

@conference{
author = "Dobričić, Vladimir and Oluić, Jelena and Nikolić, Katarina and Vučićević, Jelica and Gagić, Žarko and Filipić, Slavica and Agbaba, Danica and Čudina, Olivera",
year = "2019",
abstract = "Multi-target compounds are designed to act on at least two targets in synergistic way, in order to produce stronger biological effect. The link
between cancer and inflammation has been intensively studied in last years and inhibition of both COX-2 and 5-LOX enzymes may be an
effective therapeutic approach for colon cancer treatment [1]. Acridines are known as DNA-topoisomerase II inhibitors. These compounds
intercalate into the DNA and inhibit topoisomerase II by their side chain. Recent studies showed additional activities of acridine derivatives,
depending on the side chain structure, such as inhibition of Src, MEK and VEGFR2 kinases [2,3]. Altered activity of PI3K/mTOR signaling pathway
is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably
attractive concept in potential cancer treatment [4]. In this paper, design of three groups of multi-target compounds with potential anticancer
activity is presented. Designed compounds are potential inhibitors of COX-2 and 5-LOX, DNA-topoisomerase II complex and kinases (Src, MEK
and VEGFR2), as well as dual inhibitors of mTOR and PI3K. A set of 27 compounds with published inhibitory activity on COX-2 and 5-LOX was
formed and two QSAR models, for both activities, were created in Pentacle program. On the basis of models’ interpretation, nine new
compounds were designed and activity on both targets predicted by developed models. Twenty-three acridine derivatives were designed and
their interactions with DNA-topoisomerase II complex, Src, MEK and VEGFR2 were tested using AutoDock Vina program. Nineteen designed
compounds bind to DNA similarly to inhibitor amsacrine and among them, ten derivatives show key binding interactions with tested kinases and
therefore possess potential to inhibit them. A dataset of eighty-five compounds with dual PI3K/mTOR inhibitory activities was formed,
divided into two groups based on their structural analogy and 3D-QSAR analysis of each group was performed in Pentacle program,
9
resulting in four QSAR models. On the basis of these results, new compounds were designed and further evaluated by use of molecular
docking, virtual screening and ADMET predictions. Finally, seven compounds were chosen as the most promising new dual mTOR/PI3K inhibitors.",
publisher = "COST Action 17104 (STRATAGEM)",
journal = "STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy",
title = "Rational design of multi-target compounds with potential anticancer activity",
pages = "8-9",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5473"
}

Dobričić, V., Oluić, J., Nikolić, K., Vučićević, J., Gagić, Ž., Filipić, S., Agbaba, D.,& Čudina, O.. (2019). Rational design of multi-target compounds with potential anticancer activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy
COST Action 17104 (STRATAGEM)., 8-9.
https://hdl.handle.net/21.15107/rcub_farfar_5473

Dobričić V, Oluić J, Nikolić K, Vučićević J, Gagić Ž, Filipić S, Agbaba D, Čudina O. Rational design of multi-target compounds with potential anticancer activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy. 2019;:8-9.
https://hdl.handle.net/21.15107/rcub_farfar_5473 .

Dobričić, Vladimir, Oluić, Jelena, Nikolić, Katarina, Vučićević, Jelica, Gagić, Žarko, Filipić, Slavica, Agbaba, Danica, Čudina, Olivera, "Rational design of multi-target compounds with potential anticancer activity" in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy (2019):8-9,
https://hdl.handle.net/21.15107/rcub_farfar_5473 .

TY  - JOUR
AU  - Antonijević, Mirjana
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Oljačić, Slavica
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3013
AB  - Creation of a statistically reliable 3D-QSAR (Quantitative Structure Activity Relationships) model enables definition of the structure of the pharmacophore for antagonists of serotonin 5-HT2A receptors and selection of the key molecular determinants for the design of new antagonists. A 3D-QSAR study was applied on a series of 50 antagonists of 5-HT2A receptors. The data set is divided into the training set, composed of 33 compounds, and test set containing 14 molecules. The training set was used to build the 3D-QSAR model, while test set was used for model validation. This 3D-QSAR study was performed by use of the Pentacle 1.07 programs. Obtained statistical and validation parameters for training set (R²= 0.96; Q²=0.75, RMSEE= 0.211); and for test set (R²pred=0.51; RMSEP= 0.558); indicate on reliability and good predictive potential of the 3D-QSAR model. Based on the most influential variables of the selected 3D-QSAR model, the molecular determinants for the antagonistic effect on the 5-HT2A receptors were selected: hydrogen bond acceptor and hydrogen bond donor at a distance of 10.4A-10.8A (v495: O-N1); carbonyl oxygen and a steric hot spot at a distance of 14.8A-15.2A (v640: N1-TIP); hydrophobic domain and hydrogen bond acceptor at a distance of 3.2A-3.6A (v276: DRY-O); two steric hot spots at a distance of 18.8A-19.2A (v248: TIP-TIP) .
AB  - Formiranjem statistički pouzdanog 3D-QSAR (Quantitative Structure Activity Relationships) modela omogućeno je definisanje strukture farmakofore antagonista serotoninskih 5-HT₂A receptora i selekcija ključnih molekulskih determinanti za dizajn novih antagonista serotoninskih 5-HT₂A receptora. 3D-QSAR studija je primenjena na seriji od 50 antagonista serotoninskih 5-HT₂A receptora koji su podeljeni na trening set od 33 molekula i test set od 14 molekula. Trening set je korišćen za formiranje 3D-QSAR modela, dok je test set primenjen za validaciju modela. Za ovu 3D-QSAR studiju je upotrebljen Pentacle 1.07 program. Izračunati validacioni i statistički parametri 3D-QSAR modela (R²=0,96; Q²=0,75; RMSEE= 0,211), kao i parametri eksterne validacije na test setu (R²pred =0,51; RMSEP= 0,558), ukazuju na pouzdanost i dobru moć predviđanja izabranog 3D-QSAR modela. Na osnovu najuticajnijih varijabli izabranog 3D-QSAR modela definisana je struktura farmakofora za antagonističko dejstvo na serotoninskim 5-HT₂A receptorima: donor i akceptor vodonične veze na rastojanju od 10,4A-10,8A (v495: O-N1); karbonilni kiseonik i sterni centar na rastojanju od 14,8A-15,2A (v640: N1-TIP); hidrofobni centar i donor vodonične veze na rastojanju od 3,2A- 3,6A (v276: DRY-O); dva sterna centra na rastojanju od 18,8A-19,2A (v248: TIP-TIP).
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - 3D-QSAR modeling and pharmacophore study of serotonin 5HT-₂A receptors antagonists
T1  - 3D-QSAR modelovanje i analiza farmakofore antagonista serotoninskih 5-HT2A receptora
VL  - 67
IS  - 4
SP  - 233
EP  - 247
DO  - 10.5937/arhfarm1704233A
ER  - 

@article{
author = "Antonijević, Mirjana and Nikolić, Katarina and Vučićević, Jelica and Oljačić, Slavica and Agbaba, Danica",
year = "2017",
abstract = "Creation of a statistically reliable 3D-QSAR (Quantitative Structure Activity Relationships) model enables definition of the structure of the pharmacophore for antagonists of serotonin 5-HT2A receptors and selection of the key molecular determinants for the design of new antagonists. A 3D-QSAR study was applied on a series of 50 antagonists of 5-HT2A receptors. The data set is divided into the training set, composed of 33 compounds, and test set containing 14 molecules. The training set was used to build the 3D-QSAR model, while test set was used for model validation. This 3D-QSAR study was performed by use of the Pentacle 1.07 programs. Obtained statistical and validation parameters for training set (R²= 0.96; Q²=0.75, RMSEE= 0.211); and for test set (R²pred=0.51; RMSEP= 0.558); indicate on reliability and good predictive potential of the 3D-QSAR model. Based on the most influential variables of the selected 3D-QSAR model, the molecular determinants for the antagonistic effect on the 5-HT2A receptors were selected: hydrogen bond acceptor and hydrogen bond donor at a distance of 10.4A-10.8A (v495: O-N1); carbonyl oxygen and a steric hot spot at a distance of 14.8A-15.2A (v640: N1-TIP); hydrophobic domain and hydrogen bond acceptor at a distance of 3.2A-3.6A (v276: DRY-O); two steric hot spots at a distance of 18.8A-19.2A (v248: TIP-TIP) ., Formiranjem statistički pouzdanog 3D-QSAR (Quantitative Structure Activity Relationships) modela omogućeno je definisanje strukture farmakofore antagonista serotoninskih 5-HT₂A receptora i selekcija ključnih molekulskih determinanti za dizajn novih antagonista serotoninskih 5-HT₂A receptora. 3D-QSAR studija je primenjena na seriji od 50 antagonista serotoninskih 5-HT₂A receptora koji su podeljeni na trening set od 33 molekula i test set od 14 molekula. Trening set je korišćen za formiranje 3D-QSAR modela, dok je test set primenjen za validaciju modela. Za ovu 3D-QSAR studiju je upotrebljen Pentacle 1.07 program. Izračunati validacioni i statistički parametri 3D-QSAR modela (R²=0,96; Q²=0,75; RMSEE= 0,211), kao i parametri eksterne validacije na test setu (R²pred =0,51; RMSEP= 0,558), ukazuju na pouzdanost i dobru moć predviđanja izabranog 3D-QSAR modela. Na osnovu najuticajnijih varijabli izabranog 3D-QSAR modela definisana je struktura farmakofora za antagonističko dejstvo na serotoninskim 5-HT₂A receptorima: donor i akceptor vodonične veze na rastojanju od 10,4A-10,8A (v495: O-N1); karbonilni kiseonik i sterni centar na rastojanju od 14,8A-15,2A (v640: N1-TIP); hidrofobni centar i donor vodonične veze na rastojanju od 3,2A- 3,6A (v276: DRY-O); dva sterna centra na rastojanju od 18,8A-19,2A (v248: TIP-TIP).",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "3D-QSAR modeling and pharmacophore study of serotonin 5HT-₂A receptors antagonists, 3D-QSAR modelovanje i analiza farmakofore antagonista serotoninskih 5-HT2A receptora",
volume = "67",
number = "4",
pages = "233-247",
doi = "10.5937/arhfarm1704233A"
}

Antonijević, M., Nikolić, K., Vučićević, J., Oljačić, S.,& Agbaba, D.. (2017). 3D-QSAR modeling and pharmacophore study of serotonin 5HT-₂A receptors antagonists. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 67(4), 233-247.
https://doi.org/10.5937/arhfarm1704233A

Antonijević M, Nikolić K, Vučićević J, Oljačić S, Agbaba D. 3D-QSAR modeling and pharmacophore study of serotonin 5HT-₂A receptors antagonists. in Arhiv za farmaciju. 2017;67(4):233-247.
doi:10.5937/arhfarm1704233A .

Antonijević, Mirjana, Nikolić, Katarina, Vučićević, Jelica, Oljačić, Slavica, Agbaba, Danica, "3D-QSAR modeling and pharmacophore study of serotonin 5HT-₂A receptors antagonists" in Arhiv za farmaciju, 67, no. 4 (2017):233-247,
https://doi.org/10.5937/arhfarm1704233A . .

TY  - JOUR
AU  - Radan, Milica
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Oljačić, Slavica
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2912
AB  - All tested compounds show agonistic activity onserotonin5-HT2areceptors, which activation causes neuronal excitations, behavioral changes and platelet aggregation. The main aims of this study were to create 3D-QSAR(3D-Quantitative structure-activity relationship)model, analyse 3D-structure of the pharmacophore, validate the 3D-QSARmodel, and propose structural modification for novel 5-HT2aagonists.3D-QSAR modeling was applied to 51 agonists of 5-HT2areceptors. Dominant forms at physiologic pHof the examined compounds were optimized using the PM3 method and used for QSAR modeling. Data set was divided in two groups, training set of38 compounds, and test set of 13 compounds. Training set was used to build 3D-QSAR model, while test set was examined for the model validation. PLS (Partial Least Square Regression)method was used to develop 3D-QSAR model. Statistical parameters of the created and validated 3D-QSAR model,R2= 0.93, Q2=0.72, RMSEE=0.178, RMSEP=0.190 and R2 pred=0.63, indicate good prognostic capacity of the model.The3D-QSAR model was applied to analyse pharmacophore and to predict activity of other agonists of serotonin 5-HT2areceptors. Information obtained from the 3D-QSAR study indicated that presence of hydrogen bond donor and steric hot spot at a distance 14.80-15.20Å (v477:O-TIP), hydrophobic region and hydrogen bond donor at a distance of 2.40-2.86Å (v226:DRY-O), hydrogen bond donor and hydrogen bond acceptor at a distance of 1.60-2.00Å (v389:O-N1) and two hydrophobic regions at a distance 9.20-9.60Å (v23:DRY-DRY) are essential for agonistic activity on 5-HT2aserotonin receptors.
AB  - Ispitivana jedinjenja djeluju kao agonisti serotoninskih 5-HT2areceptora, i dovode do neuralne ekscitacije, promjene ponašanja i agregacije trombocita. Cilj ove studije je bio formiranje 3D-QSAR (3D-Quantitative structure-activity relationship) modela i 3D-strukture farmakofore agonista serotoninskih 5-HT2a receptora, validacija formiranog 3D-QSAR modela i definisanje strukturnih modifikacija za dizajn novih agonista serotoninskih 5-HT2areceptora. Iz literature su preuzete strukture i aktivnosti 51 agoniste 5-HT2areceptora. Definisani su dominantni oblici ispitivanih jedinjenja pri fiziološkom pH i optimizovane njihove konformacije primjenom PM3 (Parameterized Model revision 3) metode. Ispitivana jedinjenja su podijeljena u dvije grupe, trening set sa 38 jedinjenja i test set sa 13 jedinjenja. Trening set je korišćen za formiranje jednačine i građenje 3D-QSAR modela, a test set za validaciju 3DQSAR modela. Pomoću PLS (Partial Least Square Regression) metode kreira se novi 3DQSAR model i računaju statistički parametri modela: R2=0,93, Q2=0,72, RMSEE=0,178, RMSEP=0,190 i R2pred=0,63. Formirani i validirani 3D-QSAR model je dalje upotrijebljen za analizu 3D-strukture farmakofore i za predviđanje aktivnosti novih agonista serotoninskih 5-HT2areceptora. Analizom je utvrđeno da je za ispoljavanje agonističke aktivnosti na nivou 5-HT2a serotoninskih receptora neophodno prisustvo donora vodonične veze i sternog centra na rastojanju 14,80-15,20Å (v477:O-TIP), donora i akceptora vodonične veze na rastojanju 1,60- 2,00Å (v389:O-N1), hidrofobnog centra i donora vodonične veze na rastojanju 2,40-2,86Å (v226:DRY-O) i dva hidrofobna centra na rastojanju 9,20-9,60Å (v23:DRY-DRY).
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - 3D-QSAR study and development of pharmacophore for serotonin 5-HT2A receptors agonists
T1  - 3D-QSAR studija i razvoj farmakofore agonista serotoninskih 5-HT2A receptora
VL  - 67
IS  - 3
SP  - 165
EP  - 179
DO  - 10.5937/arhfarm1703165R
ER  - 

@article{
author = "Radan, Milica and Nikolić, Katarina and Vučićević, Jelica and Oljačić, Slavica and Agbaba, Danica",
year = "2017",
abstract = "All tested compounds show agonistic activity onserotonin5-HT2areceptors, which activation causes neuronal excitations, behavioral changes and platelet aggregation. The main aims of this study were to create 3D-QSAR(3D-Quantitative structure-activity relationship)model, analyse 3D-structure of the pharmacophore, validate the 3D-QSARmodel, and propose structural modification for novel 5-HT2aagonists.3D-QSAR modeling was applied to 51 agonists of 5-HT2areceptors. Dominant forms at physiologic pHof the examined compounds were optimized using the PM3 method and used for QSAR modeling. Data set was divided in two groups, training set of38 compounds, and test set of 13 compounds. Training set was used to build 3D-QSAR model, while test set was examined for the model validation. PLS (Partial Least Square Regression)method was used to develop 3D-QSAR model. Statistical parameters of the created and validated 3D-QSAR model,R2= 0.93, Q2=0.72, RMSEE=0.178, RMSEP=0.190 and R2 pred=0.63, indicate good prognostic capacity of the model.The3D-QSAR model was applied to analyse pharmacophore and to predict activity of other agonists of serotonin 5-HT2areceptors. Information obtained from the 3D-QSAR study indicated that presence of hydrogen bond donor and steric hot spot at a distance 14.80-15.20Å (v477:O-TIP), hydrophobic region and hydrogen bond donor at a distance of 2.40-2.86Å (v226:DRY-O), hydrogen bond donor and hydrogen bond acceptor at a distance of 1.60-2.00Å (v389:O-N1) and two hydrophobic regions at a distance 9.20-9.60Å (v23:DRY-DRY) are essential for agonistic activity on 5-HT2aserotonin receptors., Ispitivana jedinjenja djeluju kao agonisti serotoninskih 5-HT2areceptora, i dovode do neuralne ekscitacije, promjene ponašanja i agregacije trombocita. Cilj ove studije je bio formiranje 3D-QSAR (3D-Quantitative structure-activity relationship) modela i 3D-strukture farmakofore agonista serotoninskih 5-HT2a receptora, validacija formiranog 3D-QSAR modela i definisanje strukturnih modifikacija za dizajn novih agonista serotoninskih 5-HT2areceptora. Iz literature su preuzete strukture i aktivnosti 51 agoniste 5-HT2areceptora. Definisani su dominantni oblici ispitivanih jedinjenja pri fiziološkom pH i optimizovane njihove konformacije primjenom PM3 (Parameterized Model revision 3) metode. Ispitivana jedinjenja su podijeljena u dvije grupe, trening set sa 38 jedinjenja i test set sa 13 jedinjenja. Trening set je korišćen za formiranje jednačine i građenje 3D-QSAR modela, a test set za validaciju 3DQSAR modela. Pomoću PLS (Partial Least Square Regression) metode kreira se novi 3DQSAR model i računaju statistički parametri modela: R2=0,93, Q2=0,72, RMSEE=0,178, RMSEP=0,190 i R2pred=0,63. Formirani i validirani 3D-QSAR model je dalje upotrijebljen za analizu 3D-strukture farmakofore i za predviđanje aktivnosti novih agonista serotoninskih 5-HT2areceptora. Analizom je utvrđeno da je za ispoljavanje agonističke aktivnosti na nivou 5-HT2a serotoninskih receptora neophodno prisustvo donora vodonične veze i sternog centra na rastojanju 14,80-15,20Å (v477:O-TIP), donora i akceptora vodonične veze na rastojanju 1,60- 2,00Å (v389:O-N1), hidrofobnog centra i donora vodonične veze na rastojanju 2,40-2,86Å (v226:DRY-O) i dva hidrofobna centra na rastojanju 9,20-9,60Å (v23:DRY-DRY).",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "3D-QSAR study and development of pharmacophore for serotonin 5-HT2A receptors agonists, 3D-QSAR studija i razvoj farmakofore agonista serotoninskih 5-HT2A receptora",
volume = "67",
number = "3",
pages = "165-179",
doi = "10.5937/arhfarm1703165R"
}

Radan, M., Nikolić, K., Vučićević, J., Oljačić, S.,& Agbaba, D.. (2017). 3D-QSAR study and development of pharmacophore for serotonin 5-HT2A receptors agonists. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 67(3), 165-179.
https://doi.org/10.5937/arhfarm1703165R

Radan M, Nikolić K, Vučićević J, Oljačić S, Agbaba D. 3D-QSAR study and development of pharmacophore for serotonin 5-HT2A receptors agonists. in Arhiv za farmaciju. 2017;67(3):165-179.
doi:10.5937/arhfarm1703165R .

Radan, Milica, Nikolić, Katarina, Vučićević, Jelica, Oljačić, Slavica, Agbaba, Danica, "3D-QSAR study and development of pharmacophore for serotonin 5-HT2A receptors agonists" in Arhiv za farmaciju, 67, no. 3 (2017):165-179,
https://doi.org/10.5937/arhfarm1703165R . .

TY  - JOUR
AU  - Mucaji, Pavel
AU  - Atanasov, Atanas G.
AU  - Bak, Andrzej
AU  - Kozik, Violetta
AU  - Sieron, Karolina
AU  - Olsen, Mark
AU  - Pan, Weidong
AU  - Liu, Yazhou
AU  - Hu, Shengchao
AU  - Lan, Junjie
AU  - Haider, Norbert
AU  - Musiol, Robert
AU  - Vanco, Jan
AU  - Diederich, Marc
AU  - Ji, Seungwon
AU  - Zitko, Jan
AU  - Wang, Dongdong
AU  - Agbaba, Danica
AU  - Nikolić, Katarina
AU  - Oljačić, Slavica
AU  - Vučićević, Jelica
AU  - Jezova, Daniela
AU  - Tsantili-Kakoulidou, Anna
AU  - Tsopelas, Fotios
AU  - Giaginis, Constantinos
AU  - Kowalska, Teresa
AU  - Sajewicz, Mieczyslaw
AU  - Silberring, Jerzy
AU  - Mielczarek, Przemyslaw
AU  - Smoluch, Marek
AU  - Jendrzejewska, Izabela
AU  - Polanski, Jaroslaw
AU  - Jampilek, Josef
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2849
AB  - The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5-8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, Drug Synthesis and Analysis, meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.
PB  - MDPI, Basel
T2  - Molecules
T1  - The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot
VL  - 22
IS  - 11
DO  - 10.3390/molecules22111848
ER  - 

@article{
author = "Mucaji, Pavel and Atanasov, Atanas G. and Bak, Andrzej and Kozik, Violetta and Sieron, Karolina and Olsen, Mark and Pan, Weidong and Liu, Yazhou and Hu, Shengchao and Lan, Junjie and Haider, Norbert and Musiol, Robert and Vanco, Jan and Diederich, Marc and Ji, Seungwon and Zitko, Jan and Wang, Dongdong and Agbaba, Danica and Nikolić, Katarina and Oljačić, Slavica and Vučićević, Jelica and Jezova, Daniela and Tsantili-Kakoulidou, Anna and Tsopelas, Fotios and Giaginis, Constantinos and Kowalska, Teresa and Sajewicz, Mieczyslaw and Silberring, Jerzy and Mielczarek, Przemyslaw and Smoluch, Marek and Jendrzejewska, Izabela and Polanski, Jaroslaw and Jampilek, Josef",
year = "2017",
abstract = "The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5-8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, Drug Synthesis and Analysis, meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot",
volume = "22",
number = "11",
doi = "10.3390/molecules22111848"
}

Mucaji, P., Atanasov, A. G., Bak, A., Kozik, V., Sieron, K., Olsen, M., Pan, W., Liu, Y., Hu, S., Lan, J., Haider, N., Musiol, R., Vanco, J., Diederich, M., Ji, S., Zitko, J., Wang, D., Agbaba, D., Nikolić, K., Oljačić, S., Vučićević, J., Jezova, D., Tsantili-Kakoulidou, A., Tsopelas, F., Giaginis, C., Kowalska, T., Sajewicz, M., Silberring, J., Mielczarek, P., Smoluch, M., Jendrzejewska, I., Polanski, J.,& Jampilek, J.. (2017). The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot. in Molecules
MDPI, Basel., 22(11).
https://doi.org/10.3390/molecules22111848

Mucaji P, Atanasov AG, Bak A, Kozik V, Sieron K, Olsen M, Pan W, Liu Y, Hu S, Lan J, Haider N, Musiol R, Vanco J, Diederich M, Ji S, Zitko J, Wang D, Agbaba D, Nikolić K, Oljačić S, Vučićević J, Jezova D, Tsantili-Kakoulidou A, Tsopelas F, Giaginis C, Kowalska T, Sajewicz M, Silberring J, Mielczarek P, Smoluch M, Jendrzejewska I, Polanski J, Jampilek J. The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot. in Molecules. 2017;22(11).
doi:10.3390/molecules22111848 .

Mucaji, Pavel, Atanasov, Atanas G., Bak, Andrzej, Kozik, Violetta, Sieron, Karolina, Olsen, Mark, Pan, Weidong, Liu, Yazhou, Hu, Shengchao, Lan, Junjie, Haider, Norbert, Musiol, Robert, Vanco, Jan, Diederich, Marc, Ji, Seungwon, Zitko, Jan, Wang, Dongdong, Agbaba, Danica, Nikolić, Katarina, Oljačić, Slavica, Vučićević, Jelica, Jezova, Daniela, Tsantili-Kakoulidou, Anna, Tsopelas, Fotios, Giaginis, Constantinos, Kowalska, Teresa, Sajewicz, Mieczyslaw, Silberring, Jerzy, Mielczarek, Przemyslaw, Smoluch, Marek, Jendrzejewska, Izabela, Polanski, Jaroslaw, Jampilek, Josef, "The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot" in Molecules, 22, no. 11 (2017),
https://doi.org/10.3390/molecules22111848 . .

TY  - JOUR
AU  - Vučićević, Jelica
AU  - Popović, Marija
AU  - Nikolić, Katarina
AU  - Filipić, Slavica
AU  - Obradović, Darija
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2900
AB  - For this study, 31 compounds, including 16 imidazoline/alpha-adrenergic receptor (IRs/alpha-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k (BMC) and log k (wRP), respectively). Based on the retention factor (log k(wRP)) and slope of the linear curve (S) the isocratic parameter ((sic)(0)) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds. High correlations were obtained between logarithm of biopartitioning micellar chromatography (BMC) retention factor and effective permeability (r(log k(BMC) /log BB): 0.77), while for RP-HPLC system the correlations were lower (r(log k(wRP) /log BB): 0.58; r(S/log BB): -0.50; r((sic)(0) /P-e): 0.61). Based on the log k(BMC) retention data and calculated molecular parameters of the examined compounds, quantitative structure-permeability relationship (QSPR) models were developed using partial least squares, stepwise multiple linear regression, support vector machine and artificial neural network methodologies. A high degree of structural diversity of the analysed IRs/alpha-ARs ligands and CNS drugs provides wide applicability domain of the QSPR models for estimation of blood-brain barrier penetration of the related compounds.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Saudi Pharmaceutical Journal
T1  - Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis
VL  - 28
IS  - 3
SP  - 235
EP  - 252
DO  - 10.1080/1062936X.2017.1302506
ER  - 

@article{
author = "Vučićević, Jelica and Popović, Marija and Nikolić, Katarina and Filipić, Slavica and Obradović, Darija and Agbaba, Danica",
year = "2017",
abstract = "For this study, 31 compounds, including 16 imidazoline/alpha-adrenergic receptor (IRs/alpha-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k (BMC) and log k (wRP), respectively). Based on the retention factor (log k(wRP)) and slope of the linear curve (S) the isocratic parameter ((sic)(0)) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds. High correlations were obtained between logarithm of biopartitioning micellar chromatography (BMC) retention factor and effective permeability (r(log k(BMC) /log BB): 0.77), while for RP-HPLC system the correlations were lower (r(log k(wRP) /log BB): 0.58; r(S/log BB): -0.50; r((sic)(0) /P-e): 0.61). Based on the log k(BMC) retention data and calculated molecular parameters of the examined compounds, quantitative structure-permeability relationship (QSPR) models were developed using partial least squares, stepwise multiple linear regression, support vector machine and artificial neural network methodologies. A high degree of structural diversity of the analysed IRs/alpha-ARs ligands and CNS drugs provides wide applicability domain of the QSPR models for estimation of blood-brain barrier penetration of the related compounds.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Saudi Pharmaceutical Journal",
title = "Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis",
volume = "28",
number = "3",
pages = "235-252",
doi = "10.1080/1062936X.2017.1302506"
}

Vučićević, J., Popović, M., Nikolić, K., Filipić, S., Obradović, D.,& Agbaba, D.. (2017). Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis. in Saudi Pharmaceutical Journal
Taylor & Francis Ltd, Abingdon., 28(3), 235-252.
https://doi.org/10.1080/1062936X.2017.1302506

Vučićević J, Popović M, Nikolić K, Filipić S, Obradović D, Agbaba D. Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis. in Saudi Pharmaceutical Journal. 2017;28(3):235-252.
doi:10.1080/1062936X.2017.1302506 .

Vučićević, Jelica, Popović, Marija, Nikolić, Katarina, Filipić, Slavica, Obradović, Darija, Agbaba, Danica, "Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis" in Saudi Pharmaceutical Journal, 28, no. 3 (2017):235-252,
https://doi.org/10.1080/1062936X.2017.1302506 . .

TY  - CONF
AU  - Oluić, Jelena
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Gagić, Žarko
AU  - Filipić, Slavica
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2960
AB  - Phosphatidylinositol-3-kinase (PI3K) / mammalian target of rapamycin (mTOR) kinases belong to the phosphatidylinositol-3-kinase-related kinase (PIKK) family of kinases. Dysregulation of PI3K/mTOR signaling pathway is often detected in various types of malignancies and is correlated with a poor prognosis. PI3K and mTOR share considerable homology in the structure of their active sites and rational advantages of dual inhibition of PI3K/mTOR are known. In order to identify the most important structural determinants that influence antiproliferative activity, 3D-QSAR (quantitative structure activity relationship) studies were performed on two groups of structurally diverse PI3K/mTOR inhibitors. Created QSAR models passed internal and external validation allowing the reliable activity prediction of new PI3K/mTOR inhibitors that were designed based on the obtained 3D-pharmacophores. Initial pool of designed compounds was subjected to structure based virtual screening in order to select the best candidates. Results of this study may be very helpful in further discovery of selective PI3K/mTOR dual inhibitors as novel antineoplastics.
PB  - Springer-Verlag Singapore Pte Ltd, Singapore
C3  - Proceedings of the International Conference on Medical and Biological Engineering 2017 (Cmbebih 2017
T1  - QSAR modeling and structure based virtual screening of new PI3K/mTOR inhibitors as potential anticancer agents
VL  - 62
SP  - 379
EP  - 383
DO  - 10.1007/978-981-10-4166-2_58
ER  - 

@conference{
author = "Oluić, Jelena and Nikolić, Katarina and Vučićević, Jelica and Gagić, Žarko and Filipić, Slavica and Agbaba, Danica",
year = "2017",
abstract = "Phosphatidylinositol-3-kinase (PI3K) / mammalian target of rapamycin (mTOR) kinases belong to the phosphatidylinositol-3-kinase-related kinase (PIKK) family of kinases. Dysregulation of PI3K/mTOR signaling pathway is often detected in various types of malignancies and is correlated with a poor prognosis. PI3K and mTOR share considerable homology in the structure of their active sites and rational advantages of dual inhibition of PI3K/mTOR are known. In order to identify the most important structural determinants that influence antiproliferative activity, 3D-QSAR (quantitative structure activity relationship) studies were performed on two groups of structurally diverse PI3K/mTOR inhibitors. Created QSAR models passed internal and external validation allowing the reliable activity prediction of new PI3K/mTOR inhibitors that were designed based on the obtained 3D-pharmacophores. Initial pool of designed compounds was subjected to structure based virtual screening in order to select the best candidates. Results of this study may be very helpful in further discovery of selective PI3K/mTOR dual inhibitors as novel antineoplastics.",
publisher = "Springer-Verlag Singapore Pte Ltd, Singapore",
journal = "Proceedings of the International Conference on Medical and Biological Engineering 2017 (Cmbebih 2017",
title = "QSAR modeling and structure based virtual screening of new PI3K/mTOR inhibitors as potential anticancer agents",
volume = "62",
pages = "379-383",
doi = "10.1007/978-981-10-4166-2_58"
}

Oluić, J., Nikolić, K., Vučićević, J., Gagić, Ž., Filipić, S.,& Agbaba, D.. (2017). QSAR modeling and structure based virtual screening of new PI3K/mTOR inhibitors as potential anticancer agents. in Proceedings of the International Conference on Medical and Biological Engineering 2017 (Cmbebih 2017
Springer-Verlag Singapore Pte Ltd, Singapore., 62, 379-383.
https://doi.org/10.1007/978-981-10-4166-2_58

Oluić J, Nikolić K, Vučićević J, Gagić Ž, Filipić S, Agbaba D. QSAR modeling and structure based virtual screening of new PI3K/mTOR inhibitors as potential anticancer agents. in Proceedings of the International Conference on Medical and Biological Engineering 2017 (Cmbebih 2017. 2017;62:379-383.
doi:10.1007/978-981-10-4166-2_58 .

Oluić, Jelena, Nikolić, Katarina, Vučićević, Jelica, Gagić, Žarko, Filipić, Slavica, Agbaba, Danica, "QSAR modeling and structure based virtual screening of new PI3K/mTOR inhibitors as potential anticancer agents" in Proceedings of the International Conference on Medical and Biological Engineering 2017 (Cmbebih 2017, 62 (2017):379-383,
https://doi.org/10.1007/978-981-10-4166-2_58 . .

TY  - JOUR
AU  - Oluić, Jelena
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Gagić, Žarko
AU  - Filipić, Slavica
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2818
AB  - Aim and Objective: Altered activity of PI3K/mTOR signaling pathway is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably attractive concept in potential cancer treatment. The main aim of this work was to design novel PI3K/mTOR inhibitors with enhanced antiproliferative activity. Materials and Methods: 3D-QSAR pharmacophore modeling studies were performed on two groups comprised of 37 and 48 dual PI3K/mTOR inhibitors. Obtained 3D-pharmacophores were used in design of new dual PI3K/mTOR inhibitors. Based on the in silico ADMET data, structure-based virtual screening and docking studies, the most promising novel candidates were selected. Results: Four reliable PLS models with good statistical parameters (q(2) (=) 0.72, r(pred)(2) = 0.93; q(2) = 0.81, r(pred)(2) = 0.88 for 3D-QSAR (mTOR) models and q(2) = 0.79, r(pred)(2) = 0.93; q(2) = 0.79, r(pred)(2) = 0.94 for 3D-QSAR (PI3K) models) were obtained and new highly selective and potent dual PI3K/mTOR inhibitors were designed. Further in silico ADMET profiling of the designed compounds selected the most promising novel PI3K/mTOR inhibitors as drug candidates. Results of the 3D-QSAR studies were confirmed by structure-based virtual screening protocol that identified selected designed compounds as a best fit for PI3K and mTOR receptors. Molecular docking studies on PI3K and mTOR crystal structures revealed the key active site residues involved in binding of PI3K/mTOR ligands. Conclusion: After combining the results of 3D-QSAR, ADMET profiling, virtual screening and docking, compounds 56-57 and 56-62 were chosen as the most promising new dual PI3K/mTOR inhibitors.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Combinatorial Chemistry & High Throughput Screening
T1  - 3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity
VL  - 20
IS  - 4
SP  - 292
EP  - 303
DO  - 10.2174/1386207320666170427143858
ER  - 

@article{
author = "Oluić, Jelena and Nikolić, Katarina and Vučićević, Jelica and Gagić, Žarko and Filipić, Slavica and Agbaba, Danica",
year = "2017",
abstract = "Aim and Objective: Altered activity of PI3K/mTOR signaling pathway is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably attractive concept in potential cancer treatment. The main aim of this work was to design novel PI3K/mTOR inhibitors with enhanced antiproliferative activity. Materials and Methods: 3D-QSAR pharmacophore modeling studies were performed on two groups comprised of 37 and 48 dual PI3K/mTOR inhibitors. Obtained 3D-pharmacophores were used in design of new dual PI3K/mTOR inhibitors. Based on the in silico ADMET data, structure-based virtual screening and docking studies, the most promising novel candidates were selected. Results: Four reliable PLS models with good statistical parameters (q(2) (=) 0.72, r(pred)(2) = 0.93; q(2) = 0.81, r(pred)(2) = 0.88 for 3D-QSAR (mTOR) models and q(2) = 0.79, r(pred)(2) = 0.93; q(2) = 0.79, r(pred)(2) = 0.94 for 3D-QSAR (PI3K) models) were obtained and new highly selective and potent dual PI3K/mTOR inhibitors were designed. Further in silico ADMET profiling of the designed compounds selected the most promising novel PI3K/mTOR inhibitors as drug candidates. Results of the 3D-QSAR studies were confirmed by structure-based virtual screening protocol that identified selected designed compounds as a best fit for PI3K and mTOR receptors. Molecular docking studies on PI3K and mTOR crystal structures revealed the key active site residues involved in binding of PI3K/mTOR ligands. Conclusion: After combining the results of 3D-QSAR, ADMET profiling, virtual screening and docking, compounds 56-57 and 56-62 were chosen as the most promising new dual PI3K/mTOR inhibitors.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Combinatorial Chemistry & High Throughput Screening",
title = "3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity",
volume = "20",
number = "4",
pages = "292-303",
doi = "10.2174/1386207320666170427143858"
}

Oluić, J., Nikolić, K., Vučićević, J., Gagić, Ž., Filipić, S.,& Agbaba, D.. (2017). 3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity. in Combinatorial Chemistry & High Throughput Screening
Bentham Science Publ Ltd, Sharjah., 20(4), 292-303.
https://doi.org/10.2174/1386207320666170427143858

Oluić J, Nikolić K, Vučićević J, Gagić Ž, Filipić S, Agbaba D. 3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity. in Combinatorial Chemistry & High Throughput Screening. 2017;20(4):292-303.
doi:10.2174/1386207320666170427143858 .

Oluić, Jelena, Nikolić, Katarina, Vučićević, Jelica, Gagić, Žarko, Filipić, Slavica, Agbaba, Danica, "3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity" in Combinatorial Chemistry & High Throughput Screening, 20, no. 4 (2017):292-303,
https://doi.org/10.2174/1386207320666170427143858 . .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Jaćević, Vesna
AU  - Vučićević, Jelica
AU  - Nikolić, Katarina
AU  - Vladimirov, Sote
AU  - Čudina, Olivera
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3001
AB  - Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity.
PB  - Wiley-VCH Verlag GMBH, Weinheim
T2  - Archiv der Pharmazie
T1  - Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids
VL  - 350
IS  - 5
DO  - 10.1002/ardp.201600383
ER  - 

@article{
author = "Dobričić, Vladimir and Jaćević, Vesna and Vučićević, Jelica and Nikolić, Katarina and Vladimirov, Sote and Čudina, Olivera",
year = "2017",
abstract = "Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity.",
publisher = "Wiley-VCH Verlag GMBH, Weinheim",
journal = "Archiv der Pharmazie",
title = "Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids",
volume = "350",
number = "5",
doi = "10.1002/ardp.201600383"
}

Dobričić, V., Jaćević, V., Vučićević, J., Nikolić, K., Vladimirov, S.,& Čudina, O.. (2017). Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids. in Archiv der Pharmazie
Wiley-VCH Verlag GMBH, Weinheim., 350(5).
https://doi.org/10.1002/ardp.201600383

Dobričić V, Jaćević V, Vučićević J, Nikolić K, Vladimirov S, Čudina O. Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids. in Archiv der Pharmazie. 2017;350(5).
doi:10.1002/ardp.201600383 .

Dobričić, Vladimir, Jaćević, Vesna, Vučićević, Jelica, Nikolić, Katarina, Vladimirov, Sote, Čudina, Olivera, "Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids" in Archiv der Pharmazie, 350, no. 5 (2017),
https://doi.org/10.1002/ardp.201600383 . .

TY  - CONF
AU  - Vučićević, Jelica
AU  - Đoković, Nemanja
AU  - Filipić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5401
AB  - Depression is the most common psychiatric disease. There are indications that dual histamine H3 antagonsts with
selective serotonin reuptake inhibition activity could be promising novel class of more effective antidepressants.1 The
aim of this in silico study was to identify the novel dual acting antidepressants with suitable pharmacokinetic
properties, by using computer-aided drug discovery tools. Two 3D-QSAR models were developed ...
PB  - COST ACTION CA15135 (European Cooperation in Science and Technology)
C3  - COST ACTION CA15135
Multi-target paradigm for innovative ligand
identification in the drug discovery process (MuTaLig)
POLY-PHARMACOLOGY EXPANDING PAUL
EHRLICH’S MAGIC BULLET CONCEPT ,BOOK OF THE ABSTRACTS, November 19-20
T1  - Application of 3D-QSAR and virtual screening methods for design of novel antidepressants affecting serotonin transporters and histamine H3 receptors
SP  - 88
EP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5401
ER  - 

@conference{
author = "Vučićević, Jelica and Đoković, Nemanja and Filipić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "Depression is the most common psychiatric disease. There are indications that dual histamine H3 antagonsts with
selective serotonin reuptake inhibition activity could be promising novel class of more effective antidepressants.1 The
aim of this in silico study was to identify the novel dual acting antidepressants with suitable pharmacokinetic
properties, by using computer-aided drug discovery tools. Two 3D-QSAR models were developed ...",
publisher = "COST ACTION CA15135 (European Cooperation in Science and Technology)",
journal = "COST ACTION CA15135
Multi-target paradigm for innovative ligand
identification in the drug discovery process (MuTaLig)
POLY-PHARMACOLOGY EXPANDING PAUL
EHRLICH’S MAGIC BULLET CONCEPT ,BOOK OF THE ABSTRACTS, November 19-20",
title = "Application of 3D-QSAR and virtual screening methods for design of novel antidepressants affecting serotonin transporters and histamine H3 receptors",
pages = "88-88",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5401"
}

Vučićević, J., Đoković, N., Filipić, S., Nikolić, K.,& Agbaba, D.. (2016). Application of 3D-QSAR and virtual screening methods for design of novel antidepressants affecting serotonin transporters and histamine H3 receptors. in COST ACTION CA15135
Multi-target paradigm for innovative ligand
identification in the drug discovery process (MuTaLig)
POLY-PHARMACOLOGY EXPANDING PAUL
EHRLICH’S MAGIC BULLET CONCEPT ,BOOK OF THE ABSTRACTS, November 19-20
COST ACTION CA15135 (European Cooperation in Science and Technology)., 88-88.
https://hdl.handle.net/21.15107/rcub_farfar_5401

Vučićević J, Đoković N, Filipić S, Nikolić K, Agbaba D. Application of 3D-QSAR and virtual screening methods for design of novel antidepressants affecting serotonin transporters and histamine H3 receptors. in COST ACTION CA15135
Multi-target paradigm for innovative ligand
identification in the drug discovery process (MuTaLig)
POLY-PHARMACOLOGY EXPANDING PAUL
EHRLICH’S MAGIC BULLET CONCEPT ,BOOK OF THE ABSTRACTS, November 19-20. 2016;:88-88.
https://hdl.handle.net/21.15107/rcub_farfar_5401 .

Vučićević, Jelica, Đoković, Nemanja, Filipić, Slavica, Nikolić, Katarina, Agbaba, Danica, "Application of 3D-QSAR and virtual screening methods for design of novel antidepressants affecting serotonin transporters and histamine H3 receptors" in COST ACTION CA15135
Multi-target paradigm for innovative ligand
identification in the drug discovery process (MuTaLig)
POLY-PHARMACOLOGY EXPANDING PAUL
EHRLICH’S MAGIC BULLET CONCEPT ,BOOK OF THE ABSTRACTS, November 19-20 (2016):88-88,
https://hdl.handle.net/21.15107/rcub_farfar_5401 .

TY  - CONF
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Popović, Marija
AU  - Filipić, Slavica
AU  - Obradović, Darija
AU  - Dobričić, Vladimir
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5027
AB  - Imidazoline receptor ligands are a numerous
family of biologically active compounds
known to produce central hypotensive effect
by interaction with both alpha2-adrenoreceptors
(alpha2-AR) and imidazoline receptors (IRs) (1,
2).
The main aims of this study were to evaluate
Blood-Brain Barrier (BBB) permeability (Pe)
of 18 IRs/alpha-ARs ligands and 22 Central
Nervous System (CNS) drugs using Parallel
Artificial Membrane Permeability Assay
(PAMPA) and Biopartitioning Micellar
Chromatography (BMC), and than to develop
the Quantitative-Structure-Permeability
Relationship (QSPR) models useful for
prediction BBB permeability of related IRs/alpha-
ARs ligands.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia
T1  - Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling
VL  - 66
SP  - 25
EP  - 26
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5027
ER  - 

@conference{
author = "Nikolić, Katarina and Vučićević, Jelica and Popović, Marija and Filipić, Slavica and Obradović, Darija and Dobričić, Vladimir and Agbaba, Danica",
year = "2016",
abstract = "Imidazoline receptor ligands are a numerous
family of biologically active compounds
known to produce central hypotensive effect
by interaction with both alpha2-adrenoreceptors
(alpha2-AR) and imidazoline receptors (IRs) (1,
2).
The main aims of this study were to evaluate
Blood-Brain Barrier (BBB) permeability (Pe)
of 18 IRs/alpha-ARs ligands and 22 Central
Nervous System (CNS) drugs using Parallel
Artificial Membrane Permeability Assay
(PAMPA) and Biopartitioning Micellar
Chromatography (BMC), and than to develop
the Quantitative-Structure-Permeability
Relationship (QSPR) models useful for
prediction BBB permeability of related IRs/alpha-
ARs ligands.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia",
title = "Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling",
volume = "66",
pages = "25-26",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5027"
}

Nikolić, K., Vučićević, J., Popović, M., Filipić, S., Obradović, D., Dobričić, V.,& Agbaba, D.. (2016). Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling. in Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia
Savez farmaceutskih udruženja Srbije, Beograd., 66, 25-26.
https://hdl.handle.net/21.15107/rcub_farfar_5027

Nikolić K, Vučićević J, Popović M, Filipić S, Obradović D, Dobričić V, Agbaba D. Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling. in Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia. 2016;66:25-26.
https://hdl.handle.net/21.15107/rcub_farfar_5027 .

Nikolić, Katarina, Vučićević, Jelica, Popović, Marija, Filipić, Slavica, Obradović, Darija, Dobričić, Vladimir, Agbaba, Danica, "Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling" in Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia, 66 (2016):25-26,
https://hdl.handle.net/21.15107/rcub_farfar_5027 .

TY  - JOUR
AU  - Gagić, Žarko
AU  - Ivković, Branka
AU  - Srdić-Rajić, Tatjana
AU  - Vučićević, Jelica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2532
AB  - Tocopherols and tocotrienols belong to the family of vitamin E (VE) with the well-known antioxidant properties. For certain alpha-tocopherol and gamma-tocotrienol derivatives used as the lead compounds in this study, antitumor activities against various cancer cell types have been reported. In the course of the last decade, structural analogs of VE (esters, ethers and amides) with an enhanced antiproliferative and proapoptotic activity against various cancer cells were synthesized. Within the framework of this study, seven amino acid esters of alpha-tocopherol (4a-d) and gamma-tocotrienol (6a-c) were prepared using the EDC/DMAP reaction conditions and their ability to inhibit proliferation of the MCF-7 and MDA-MB-231 breast cancer cells and the A549 lung cancer cells was evaluated. Compound 6a showed an activity against all three cell lines (IC50: 20.6 mu M, 28.6 mu M and 19 mu M for the MCF-7, MDA-MB-231 and A549 cells, respectively), while compound 4a inhibited proliferation of the MCF-7 (IC50 = 8.6 mu M) and A549 cells (IC50 = 8.6 mu M). Ester 4d exerted strong antiproliferative activity against the estrogenunresponsive, multi-drug resistant MDA-MB-231 breast cancer cell line, with IC50 value of 9.2 mu M. Compared with the strong activity of compounds 4a, 4d and 6a, commercial alpha-tocopheryl succinate and gamma-tocotrienol showed only a limited activity against all three cell lines, with IC50 values >50 mu M. Investigation of the cell cycle phase distribution and the cell death induction confirmed an apoptosis of the MDA-MB-231 cells treated with 4d, as well as a synergistic effect of 4d with the known anticancer drug doxorubicin. This result suggests a possibility of a combined therapy of breast cancer in order to improve the therapeutic response and to lower the toxicity associated with a high dose of doxorubicin. The stability study of 4d in human plasma showed that ca. 83% initial concentration of this compound remains in plasma in the course of six hours incubation. The ligand based virtual screening of the ChEMBL database identified new compounds with a potential antiproliferative activity on MCF-7 and on multi-drug resistant MDA-MB 231 breast cancer cells.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs
VL  - 88
SP  - 59
EP  - 69
DO  - 10.1016/j.ejps.2016.04.008
ER  - 

@article{
author = "Gagić, Žarko and Ivković, Branka and Srdić-Rajić, Tatjana and Vučićević, Jelica and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "Tocopherols and tocotrienols belong to the family of vitamin E (VE) with the well-known antioxidant properties. For certain alpha-tocopherol and gamma-tocotrienol derivatives used as the lead compounds in this study, antitumor activities against various cancer cell types have been reported. In the course of the last decade, structural analogs of VE (esters, ethers and amides) with an enhanced antiproliferative and proapoptotic activity against various cancer cells were synthesized. Within the framework of this study, seven amino acid esters of alpha-tocopherol (4a-d) and gamma-tocotrienol (6a-c) were prepared using the EDC/DMAP reaction conditions and their ability to inhibit proliferation of the MCF-7 and MDA-MB-231 breast cancer cells and the A549 lung cancer cells was evaluated. Compound 6a showed an activity against all three cell lines (IC50: 20.6 mu M, 28.6 mu M and 19 mu M for the MCF-7, MDA-MB-231 and A549 cells, respectively), while compound 4a inhibited proliferation of the MCF-7 (IC50 = 8.6 mu M) and A549 cells (IC50 = 8.6 mu M). Ester 4d exerted strong antiproliferative activity against the estrogenunresponsive, multi-drug resistant MDA-MB-231 breast cancer cell line, with IC50 value of 9.2 mu M. Compared with the strong activity of compounds 4a, 4d and 6a, commercial alpha-tocopheryl succinate and gamma-tocotrienol showed only a limited activity against all three cell lines, with IC50 values >50 mu M. Investigation of the cell cycle phase distribution and the cell death induction confirmed an apoptosis of the MDA-MB-231 cells treated with 4d, as well as a synergistic effect of 4d with the known anticancer drug doxorubicin. This result suggests a possibility of a combined therapy of breast cancer in order to improve the therapeutic response and to lower the toxicity associated with a high dose of doxorubicin. The stability study of 4d in human plasma showed that ca. 83% initial concentration of this compound remains in plasma in the course of six hours incubation. The ligand based virtual screening of the ChEMBL database identified new compounds with a potential antiproliferative activity on MCF-7 and on multi-drug resistant MDA-MB 231 breast cancer cells.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs",
volume = "88",
pages = "59-69",
doi = "10.1016/j.ejps.2016.04.008"
}

Gagić, Ž., Ivković, B., Srdić-Rajić, T., Vučićević, J., Nikolić, K.,& Agbaba, D.. (2016). Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 88, 59-69.
https://doi.org/10.1016/j.ejps.2016.04.008

Gagić Ž, Ivković B, Srdić-Rajić T, Vučićević J, Nikolić K, Agbaba D. Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs. in European Journal of Pharmaceutical Sciences. 2016;88:59-69.
doi:10.1016/j.ejps.2016.04.008 .

Gagić, Žarko, Ivković, Branka, Srdić-Rajić, Tatjana, Vučićević, Jelica, Nikolić, Katarina, Agbaba, Danica, "Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs" in European Journal of Pharmaceutical Sciences, 88 (2016):59-69,
https://doi.org/10.1016/j.ejps.2016.04.008 . .

TY  - CONF
AU  - Filipić, Slavica
AU  - Ružić, Dušan
AU  - Vučićević, Jelica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4914
AB  - The retention properties of 22 selected imidazoline receptor ligands were studied by high-performance liquid chromatography on α1-acid glycoprotein (AGP) column using 2-propanol as organic additive and Sørensen phosphate buffer (pH 7.0). Linear solvation energy relationships (LSER) were built using isocratic retention factors - log k5, log k8, log k10, log k12, log k15 obtained for (5, 8, 10, 12, 15)% of 2- propanol in mobile phase, respectively and extrapolated log Kw values as dependant variables. Independent variables (Abraham descriptors) for LSER analysis were calculated by ACD/i-Lab software. LSER analysis indicated on McGowan volume, hydrogen bond basicity and excess molar refraction as the most important parameters for all isocratic retention factors and log Kw values of 22 selected imidazoline receptor ligands.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
T1  - Linear solvation energy relationship study of selected imidazoline receptor ligands on α1-acid glycoprotein column
VL  - II
SP  - 821
EP  - 824
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4914
ER  - 

@conference{
author = "Filipić, Slavica and Ružić, Dušan and Vučićević, Jelica and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "The retention properties of 22 selected imidazoline receptor ligands were studied by high-performance liquid chromatography on α1-acid glycoprotein (AGP) column using 2-propanol as organic additive and Sørensen phosphate buffer (pH 7.0). Linear solvation energy relationships (LSER) were built using isocratic retention factors - log k5, log k8, log k10, log k12, log k15 obtained for (5, 8, 10, 12, 15)% of 2- propanol in mobile phase, respectively and extrapolated log Kw values as dependant variables. Independent variables (Abraham descriptors) for LSER analysis were calculated by ACD/i-Lab software. LSER analysis indicated on McGowan volume, hydrogen bond basicity and excess molar refraction as the most important parameters for all isocratic retention factors and log Kw values of 22 selected imidazoline receptor ligands.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia",
title = "Linear solvation energy relationship study of selected imidazoline receptor ligands on α1-acid glycoprotein column",
volume = "II",
pages = "821-824",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4914"
}

Filipić, S., Ružić, D., Vučićević, J., Nikolić, K.,& Agbaba, D.. (2016). Linear solvation energy relationship study of selected imidazoline receptor ligands on α1-acid glycoprotein column. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
Society of Physical Chemists of Serbia., II, 821-824.
https://hdl.handle.net/21.15107/rcub_farfar_4914

Filipić S, Ružić D, Vučićević J, Nikolić K, Agbaba D. Linear solvation energy relationship study of selected imidazoline receptor ligands on α1-acid glycoprotein column. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia. 2016;II:821-824.
https://hdl.handle.net/21.15107/rcub_farfar_4914 .

Filipić, Slavica, Ružić, Dušan, Vučićević, Jelica, Nikolić, Katarina, Agbaba, Danica, "Linear solvation energy relationship study of selected imidazoline receptor ligands on α1-acid glycoprotein column" in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia, II (2016):821-824,
https://hdl.handle.net/21.15107/rcub_farfar_4914 .

TY  - JOUR
AU  - Filipić, Slavica
AU  - Ružić, Dušan
AU  - Vučićević, Jelica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2740
AB  - The retention behaviour of 22 selected imidazoline drugs and derivatives was investigated on alpha(1)-acid glycoprotein (AGP) column using Sorensen phosphate buffer (pH 7.0) and 2-propanol as organic modifier. Quantitative Structure-Retention Relationships (QSRR) models were built using extrapolated logick(w), values as well as isocratic retention factors (logk(5), logk(8), logk(10) logk(12), logk(15) obtained for 5%, 8%, 10%, 12%, and 15%, of 2-propanol in mobile phase, respectively) as dependant variables and calculated physicochemical parameters as independant variables. The established QSRR models were built by stepwise multiple linear regression (MLR) and partial least squares regression (PLS). The performance of the stepwise and PIS models was tested by cross-validation and the external test set prediction. The validated QSRR models were compared and the optimal PLS-QSRR model for logk(w) and each isocratic retention factors (PLS-QSRR(logk(5)), PLS-QSRR(logk(8)), PLS-QSRR(logk(10)), MLR-QSRR(logk(12)), MLR-QSRR(logk(15))) were selected. The QSRR results were further confirmed by Linear Salvation Energy Relationships (LSER). LSER analysis indicated on hydrogen bond basicity, McGowan volume and excess molar refraction as the most significant parameters for all AGP chromatographic retention factors and logk(w) values of 22 selected imidazoline drugs and derivatives.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Quantitative structure-retention relationship of selected imidazoline derivatives on alpha(1)-acid glycoprotein column
VL  - 127
SP  - 101
EP  - 111
DO  - 10.1016/j.jpba.2016.02.053
ER  - 

@article{
author = "Filipić, Slavica and Ružić, Dušan and Vučićević, Jelica and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "The retention behaviour of 22 selected imidazoline drugs and derivatives was investigated on alpha(1)-acid glycoprotein (AGP) column using Sorensen phosphate buffer (pH 7.0) and 2-propanol as organic modifier. Quantitative Structure-Retention Relationships (QSRR) models were built using extrapolated logick(w), values as well as isocratic retention factors (logk(5), logk(8), logk(10) logk(12), logk(15) obtained for 5%, 8%, 10%, 12%, and 15%, of 2-propanol in mobile phase, respectively) as dependant variables and calculated physicochemical parameters as independant variables. The established QSRR models were built by stepwise multiple linear regression (MLR) and partial least squares regression (PLS). The performance of the stepwise and PIS models was tested by cross-validation and the external test set prediction. The validated QSRR models were compared and the optimal PLS-QSRR model for logk(w) and each isocratic retention factors (PLS-QSRR(logk(5)), PLS-QSRR(logk(8)), PLS-QSRR(logk(10)), MLR-QSRR(logk(12)), MLR-QSRR(logk(15))) were selected. The QSRR results were further confirmed by Linear Salvation Energy Relationships (LSER). LSER analysis indicated on hydrogen bond basicity, McGowan volume and excess molar refraction as the most significant parameters for all AGP chromatographic retention factors and logk(w) values of 22 selected imidazoline drugs and derivatives.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Quantitative structure-retention relationship of selected imidazoline derivatives on alpha(1)-acid glycoprotein column",
volume = "127",
pages = "101-111",
doi = "10.1016/j.jpba.2016.02.053"
}

Filipić, S., Ružić, D., Vučićević, J., Nikolić, K.,& Agbaba, D.. (2016). Quantitative structure-retention relationship of selected imidazoline derivatives on alpha(1)-acid glycoprotein column. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 127, 101-111.
https://doi.org/10.1016/j.jpba.2016.02.053

Filipić S, Ružić D, Vučićević J, Nikolić K, Agbaba D. Quantitative structure-retention relationship of selected imidazoline derivatives on alpha(1)-acid glycoprotein column. in Journal of Pharmaceutical and Biomedical Analysis. 2016;127:101-111.
doi:10.1016/j.jpba.2016.02.053 .

Filipić, Slavica, Ružić, Dušan, Vučićević, Jelica, Nikolić, Katarina, Agbaba, Danica, "Quantitative structure-retention relationship of selected imidazoline derivatives on alpha(1)-acid glycoprotein column" in Journal of Pharmaceutical and Biomedical Analysis, 127 (2016):101-111,
https://doi.org/10.1016/j.jpba.2016.02.053 . .

TY  - JOUR
AU  - Vučićević, Jelica
AU  - Srdić-Rajić, Tatjana
AU  - Pieroni, Marco
AU  - Laurila, Jonne M. M.
AU  - Perović, Vladimir
AU  - Tassini, Sabrina
AU  - Azzali, Elisa
AU  - Costantino, Gabriele
AU  - Glisić, Sanja
AU  - Agbaba, Danica
AU  - Scheinin, Mika
AU  - Nikolić, Katarina
AU  - Radi, Marco
AU  - Veljković, Nevena
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2526
AB  - The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I-1-type imidazoline receptors (I-1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from alpha(2)-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine- derived compounds with anticancer potential and devoid of alpha(2)-adrenoceptor effects by means of ligand-and structure-based drug design approaches. Starting from a large virtual library, eleven compounds were selected, synthesized and submitted to biological evaluation. The most active compound 5 exhibited a cytotoxic profile similar to that of rilmenidine, but without appreciable affinity to alpha(2)-adrenoceptors. In addition, compound 5 significantly enhanced the apoptotic response to doxorubicin, and may thus represent an important tool for the development of better adjuvant chemotherapeutic strategies for doxorubicin-insensitive cancers.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & Medicinal Chemistry
T1  - A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin
VL  - 24
IS  - 14
SP  - 3174
EP  - 3183
DO  - 10.1016/j.bmc.2016.05.043
ER  - 

@article{
author = "Vučićević, Jelica and Srdić-Rajić, Tatjana and Pieroni, Marco and Laurila, Jonne M. M. and Perović, Vladimir and Tassini, Sabrina and Azzali, Elisa and Costantino, Gabriele and Glisić, Sanja and Agbaba, Danica and Scheinin, Mika and Nikolić, Katarina and Radi, Marco and Veljković, Nevena",
year = "2016",
abstract = "The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I-1-type imidazoline receptors (I-1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from alpha(2)-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine- derived compounds with anticancer potential and devoid of alpha(2)-adrenoceptor effects by means of ligand-and structure-based drug design approaches. Starting from a large virtual library, eleven compounds were selected, synthesized and submitted to biological evaluation. The most active compound 5 exhibited a cytotoxic profile similar to that of rilmenidine, but without appreciable affinity to alpha(2)-adrenoceptors. In addition, compound 5 significantly enhanced the apoptotic response to doxorubicin, and may thus represent an important tool for the development of better adjuvant chemotherapeutic strategies for doxorubicin-insensitive cancers.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & Medicinal Chemistry",
title = "A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin",
volume = "24",
number = "14",
pages = "3174-3183",
doi = "10.1016/j.bmc.2016.05.043"
}

Vučićević, J., Srdić-Rajić, T., Pieroni, M., Laurila, J. M. M., Perović, V., Tassini, S., Azzali, E., Costantino, G., Glisić, S., Agbaba, D., Scheinin, M., Nikolić, K., Radi, M.,& Veljković, N.. (2016). A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. in Bioorganic & Medicinal Chemistry
Pergamon-Elsevier Science Ltd, Oxford., 24(14), 3174-3183.
https://doi.org/10.1016/j.bmc.2016.05.043

Vučićević J, Srdić-Rajić T, Pieroni M, Laurila JMM, Perović V, Tassini S, Azzali E, Costantino G, Glisić S, Agbaba D, Scheinin M, Nikolić K, Radi M, Veljković N. A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. in Bioorganic & Medicinal Chemistry. 2016;24(14):3174-3183.
doi:10.1016/j.bmc.2016.05.043 .

Vučićević, Jelica, Srdić-Rajić, Tatjana, Pieroni, Marco, Laurila, Jonne M. M., Perović, Vladimir, Tassini, Sabrina, Azzali, Elisa, Costantino, Gabriele, Glisić, Sanja, Agbaba, Danica, Scheinin, Mika, Nikolić, Katarina, Radi, Marco, Veljković, Nevena, "A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin" in Bioorganic & Medicinal Chemistry, 24, no. 14 (2016):3174-3183,
https://doi.org/10.1016/j.bmc.2016.05.043 . .

TY  - JOUR
AU  - Nikolić, Katarina
AU  - Mavridis, Lazaros
AU  - Đikić, Teodora
AU  - Vučićević, Jelica
AU  - Agbaba, Danica
AU  - Yelekci, Kemal
AU  - Mitchell, John B. O.
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2540
AB  - The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug discovery programs. A probabilistic method, the ParzenRosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D-1-R/D-2-R/5-HT2A-R/H-3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Neuroscience
T1  - Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies
VL  - 10
DO  - 10.3389/fnins.2016.00265
ER  - 

@article{
author = "Nikolić, Katarina and Mavridis, Lazaros and Đikić, Teodora and Vučićević, Jelica and Agbaba, Danica and Yelekci, Kemal and Mitchell, John B. O.",
year = "2016",
abstract = "The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug discovery programs. A probabilistic method, the ParzenRosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D-1-R/D-2-R/5-HT2A-R/H-3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Neuroscience",
title = "Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies",
volume = "10",
doi = "10.3389/fnins.2016.00265"
}

Nikolić, K., Mavridis, L., Đikić, T., Vučićević, J., Agbaba, D., Yelekci, K.,& Mitchell, J. B. O.. (2016). Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies. in Frontiers in Neuroscience
Frontiers Media Sa, Lausanne., 10.
https://doi.org/10.3389/fnins.2016.00265

Nikolić K, Mavridis L, Đikić T, Vučićević J, Agbaba D, Yelekci K, Mitchell JBO. Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies. in Frontiers in Neuroscience. 2016;10.
doi:10.3389/fnins.2016.00265 .

Nikolić, Katarina, Mavridis, Lazaros, Đikić, Teodora, Vučićević, Jelica, Agbaba, Danica, Yelekci, Kemal, Mitchell, John B. O., "Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies" in Frontiers in Neuroscience, 10 (2016),
https://doi.org/10.3389/fnins.2016.00265 . .

TY  - CONF
AU  - Vučićević, Jelica
AU  - Nikolić, Katarina
AU  - Popović, Marija
AU  - Filipić, Slavica
AU  - Agbaba, Danica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5047
AB  - Blood-Brain Barrier (BBB) plays an essential role in protecting Central Nervous System (CNS) from harmful agents present in the bloodstream. In order to estimate central nervous delivery of compounds a lot of useful in vitro models have been developed. ...
PB  - National Institute of Chemistry, Slovenia
C3  - 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS
T1  - The use of biopartitioning micellar chromatography for determination of BBB penetration of alpha-adrenergic/imidazoline receptor ligands
SP  - 54
EP  - 54
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5047
ER  - 

@conference{
author = "Vučićević, Jelica and Nikolić, Katarina and Popović, Marija and Filipić, Slavica and Agbaba, Danica",
year = "2015",
abstract = "Blood-Brain Barrier (BBB) plays an essential role in protecting Central Nervous System (CNS) from harmful agents present in the bloodstream. In order to estimate central nervous delivery of compounds a lot of useful in vitro models have been developed. ...",
publisher = "National Institute of Chemistry, Slovenia",
journal = "21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS",
title = "The use of biopartitioning micellar chromatography for determination of BBB penetration of alpha-adrenergic/imidazoline receptor ligands",
pages = "54-54",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5047"
}

Vučićević, J., Nikolić, K., Popović, M., Filipić, S.,& Agbaba, D.. (2015). The use of biopartitioning micellar chromatography for determination of BBB penetration of alpha-adrenergic/imidazoline receptor ligands. in 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS
National Institute of Chemistry, Slovenia., 54-54.
https://hdl.handle.net/21.15107/rcub_farfar_5047

Vučićević J, Nikolić K, Popović M, Filipić S, Agbaba D. The use of biopartitioning micellar chromatography for determination of BBB penetration of alpha-adrenergic/imidazoline receptor ligands. in 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS. 2015;:54-54.
https://hdl.handle.net/21.15107/rcub_farfar_5047 .

Vučićević, Jelica, Nikolić, Katarina, Popović, Marija, Filipić, Slavica, Agbaba, Danica, "The use of biopartitioning micellar chromatography for determination of BBB penetration of alpha-adrenergic/imidazoline receptor ligands" in 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS (2015):54-54,
https://hdl.handle.net/21.15107/rcub_farfar_5047 .

TY  - JOUR
AU  - Vučićević, Jelica
AU  - Nikolić, Katarina
AU  - Dobričić, Vladimir
AU  - Agbaba, Danica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2380
AB  - Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both alpha(2)-adrenoreceptors (alpha(2)-AR) and imidazoline receptors (IRs). Recent hypotheses connect those ligands with several neurological disorders. Therefore some IRs ligands are examined as novel centrally acting antihypertensives and drug candidates for treatment of various neurological diseases. Effective Blood-Brain Barrier (BBB) permeability (P-e) of 18 IRs/alpha-ARs ligands and 22 Central Nervous System (CNS) drugs was experimentally determined using Parallel Artificial Membrane Permeability Assay (PAMPA) and studied by the Quantitative-Structure-Permeability Relationship (QSPR) methodology. The dominant molecules/cations species of compounds have been calculated at pH = 7.4. The analyzed ligands were optimized using Density Functional Theory (B3LYP/6-31G(d,p)) included in ChemBio3D Ultra 13.0 program and molecule descriptors for optimized compounds were calculated using ChemBio3D Ultra 13.0, Dragon 6.0 and ADMET predictor 6.5 software. Effective permeability of compounds was used as dependent variable (Y), while calculated molecular parametres were used as independent variables (X) in the QSPR study. SIMCA P+ 12.0 was used for Partial Least Square (PLS) analysis, while the stepwise Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) modeling were performed using STASTICA Neural Networks 4.0. Predictive potential of the formed models was confirmed by Leave-One-Out Cross- and external-validation and the most reliable models were selected. The descriptors that are important for model building are identified as well as their influence on BBB permeability. Results of the QSPR studies could be used as time and cost efficient screening tools for evaluation of BBB permeation of novel alpha-adrenergic/imidazoline receptor ligands, as promising drug candidates for treatment of hypertension or neurological diseases.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Prediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis
VL  - 68
SP  - 94
EP  - 105
DO  - 10.1016/j.ejps.2014.12.014
ER  - 

@article{
author = "Vučićević, Jelica and Nikolić, Katarina and Dobričić, Vladimir and Agbaba, Danica",
year = "2015",
abstract = "Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both alpha(2)-adrenoreceptors (alpha(2)-AR) and imidazoline receptors (IRs). Recent hypotheses connect those ligands with several neurological disorders. Therefore some IRs ligands are examined as novel centrally acting antihypertensives and drug candidates for treatment of various neurological diseases. Effective Blood-Brain Barrier (BBB) permeability (P-e) of 18 IRs/alpha-ARs ligands and 22 Central Nervous System (CNS) drugs was experimentally determined using Parallel Artificial Membrane Permeability Assay (PAMPA) and studied by the Quantitative-Structure-Permeability Relationship (QSPR) methodology. The dominant molecules/cations species of compounds have been calculated at pH = 7.4. The analyzed ligands were optimized using Density Functional Theory (B3LYP/6-31G(d,p)) included in ChemBio3D Ultra 13.0 program and molecule descriptors for optimized compounds were calculated using ChemBio3D Ultra 13.0, Dragon 6.0 and ADMET predictor 6.5 software. Effective permeability of compounds was used as dependent variable (Y), while calculated molecular parametres were used as independent variables (X) in the QSPR study. SIMCA P+ 12.0 was used for Partial Least Square (PLS) analysis, while the stepwise Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) modeling were performed using STASTICA Neural Networks 4.0. Predictive potential of the formed models was confirmed by Leave-One-Out Cross- and external-validation and the most reliable models were selected. The descriptors that are important for model building are identified as well as their influence on BBB permeability. Results of the QSPR studies could be used as time and cost efficient screening tools for evaluation of BBB permeation of novel alpha-adrenergic/imidazoline receptor ligands, as promising drug candidates for treatment of hypertension or neurological diseases.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Prediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis",
volume = "68",
pages = "94-105",
doi = "10.1016/j.ejps.2014.12.014"
}

Vučićević, J., Nikolić, K., Dobričić, V.,& Agbaba, D.. (2015). Prediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 68, 94-105.
https://doi.org/10.1016/j.ejps.2014.12.014

Vučićević J, Nikolić K, Dobričić V, Agbaba D. Prediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis. in European Journal of Pharmaceutical Sciences. 2015;68:94-105.
doi:10.1016/j.ejps.2014.12.014 .

Vučićević, Jelica, Nikolić, Katarina, Dobričić, Vladimir, Agbaba, Danica, "Prediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis" in European Journal of Pharmaceutical Sciences, 68 (2015):94-105,
https://doi.org/10.1016/j.ejps.2014.12.014 . .