TY  - CONF
AU  - Beljkaš, Milan
AU  - Rebić, Jelena
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5043
AB  - Rho-associated coiled-coil kinases (ROCKs) are involved in essential
cellular functions such as adhesion, contraction, motility, proliferation, and cell
survival/apoptosis. Four ROCK inhibitors have already been approved by the FDA and
are used to treat glaucoma (ripasudil and netarsudil), cerebral vasospasm (fasudil), and
graft-versus-host disease (belumosudil). Recent studies have focused on exploring the
role of ROCK kinase inhibitors in cancer treatment and the development of new ROCK
inhibitors. The main objective of this study was to identify critical structural features
relevant to the inhibition of ROCK1 using a ligand-based 3D-QSAR (3D quantitative
structure-activity relationship) method. The 3D-QSAR model for ROCK1 was created
and validated using internal and external validation parameters (R2, Q2, R2pred, rm2, r/2m, 𝑟���������𝑚���������
2̅̅̅
and ∆r2m). The main structural features that correlate with the inhibition of ROCK1 were
identified (e.g., heterocycle with hydrogen donor group like nitrogen atom) and further
structural modifications of the ROCK1 inhibitors that contribute to increased activity
were proposed (removal of the amino group of the oxadiazole, modification of the
substituents of the phenyl ring).
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS
T1  - 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors
SP  - 1584
EP  - 1588
DO  - 10.46793/ICCBI23.584B
ER  - 

@conference{
author = "Beljkaš, Milan and Rebić, Jelena and Radan, Milica and Đikić, Teodora and Oljačić, Slavica and Nikolić, Katarina",
year = "2023",
abstract = "Rho-associated coiled-coil kinases (ROCKs) are involved in essential
cellular functions such as adhesion, contraction, motility, proliferation, and cell
survival/apoptosis. Four ROCK inhibitors have already been approved by the FDA and
are used to treat glaucoma (ripasudil and netarsudil), cerebral vasospasm (fasudil), and
graft-versus-host disease (belumosudil). Recent studies have focused on exploring the
role of ROCK kinase inhibitors in cancer treatment and the development of new ROCK
inhibitors. The main objective of this study was to identify critical structural features
relevant to the inhibition of ROCK1 using a ligand-based 3D-QSAR (3D quantitative
structure-activity relationship) method. The 3D-QSAR model for ROCK1 was created
and validated using internal and external validation parameters (R2, Q2, R2pred, rm2, r/2m, 𝑟���������𝑚���������
2̅̅̅
and ∆r2m). The main structural features that correlate with the inhibition of ROCK1 were
identified (e.g., heterocycle with hydrogen donor group like nitrogen atom) and further
structural modifications of the ROCK1 inhibitors that contribute to increased activity
were proposed (removal of the amino group of the oxadiazole, modification of the
substituents of the phenyl ring).",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS",
title = "3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors",
pages = "1584-1588",
doi = "10.46793/ICCBI23.584B"
}

Beljkaš, M., Rebić, J., Radan, M., Đikić, T., Oljačić, S.,& Nikolić, K.. (2023). 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 1584-1588.
https://doi.org/10.46793/ICCBI23.584B

Beljkaš M, Rebić J, Radan M, Đikić T, Oljačić S, Nikolić K. 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS. 2023;:1584-1588.
doi:10.46793/ICCBI23.584B .

Beljkaš, Milan, Rebić, Jelena, Radan, Milica, Đikić, Teodora, Oljačić, Slavica, Nikolić, Katarina, "3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors" in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS (2023):1584-1588,
https://doi.org/10.46793/ICCBI23.584B . .

TY  - CONF
AU  - Beljkaš, Milan
AU  - Rebić, Jelena
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5041
AB  - Overexpression of Rho-associated protein kinases has been associated with various
diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment.
However, some of them have been shown to have anti-tumor potential. The main objective of this
study was to develop novel ROCK1 inhibitors using the structure-based method, molecular
docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key
interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds
between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating
possible structural changes in the hinge region of studied compounds. On the other hand, the
lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising
approach for further structural modifications in order to design more effective ROCK1 inhibitors.
All the important interactions between the developed ROCK1 inhibitors and the binding site
of the enzyme were established. They also showed acceptable pharmacokinetic properties and
could be further used for synthesis and evaluation by various biological assays.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
T1  - Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors
SP  - 1589
EP  - 1592
DO  - 10.46793/ICCBI23.589B
ER  - 

@conference{
author = "Beljkaš, Milan and Rebić, Jelena and Radan, Milica and Đikić, Teodora and Oljačić, Slavica and Nikolić, Katarina",
year = "2023",
abstract = "Overexpression of Rho-associated protein kinases has been associated with various
diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment.
However, some of them have been shown to have anti-tumor potential. The main objective of this
study was to develop novel ROCK1 inhibitors using the structure-based method, molecular
docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key
interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds
between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating
possible structural changes in the hinge region of studied compounds. On the other hand, the
lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising
approach for further structural modifications in order to design more effective ROCK1 inhibitors.
All the important interactions between the developed ROCK1 inhibitors and the binding site
of the enzyme were established. They also showed acceptable pharmacokinetic properties and
could be further used for synthesis and evaluation by various biological assays.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS",
title = "Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors",
pages = "1589-1592",
doi = "10.46793/ICCBI23.589B"
}

Beljkaš, M., Rebić, J., Radan, M., Đikić, T., Oljačić, S.,& Nikolić, K.. (2023). Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 1589-1592.
https://doi.org/10.46793/ICCBI23.589B

Beljkaš M, Rebić J, Radan M, Đikić T, Oljačić S, Nikolić K. Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS. 2023;:1589-1592.
doi:10.46793/ICCBI23.589B .

Beljkaš, Milan, Rebić, Jelena, Radan, Milica, Đikić, Teodora, Oljačić, Slavica, Nikolić, Katarina, "Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS (2023):1589-1592,
https://doi.org/10.46793/ICCBI23.589B . .

TY  - CONF
AU  - Nikolić, Katarina
AU  - Radan, Milica
AU  - Đikić, Teodora
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4762
PB  - European Research Network on Signal Transduction CA18133 (ERNEST)
C3  - 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece
T1  - Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders
SP  - 125
EP  - 125
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4762
ER  - 

@conference{
author = "Nikolić, Katarina and Radan, Milica and Đikić, Teodora",
year = "2023",
publisher = "European Research Network on Signal Transduction CA18133 (ERNEST)",
journal = "8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece",
title = "Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders",
pages = "125-125",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4762"
}

Nikolić, K., Radan, M.,& Đikić, T.. (2023). Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders. in 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece
European Research Network on Signal Transduction CA18133 (ERNEST)., 125-125.
https://hdl.handle.net/21.15107/rcub_farfar_4762

Nikolić K, Radan M, Đikić T. Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders. in 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece. 2023;:125-125.
https://hdl.handle.net/21.15107/rcub_farfar_4762 .

Nikolić, Katarina, Radan, Milica, Đikić, Teodora, "Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders" in 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece (2023):125-125,
https://hdl.handle.net/21.15107/rcub_farfar_4762 .

TY  - JOUR
AU  - Obradović, Darija
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4045
AB  - The drug-human serum albumin binding interaction was evaluated on a stationary phase immobilized with human serum albumin using a mixture of phosphate buffer (pH 7.0) and acetonitrile modifier as mobile phase. The 33 compounds that have a wide structural and therapeutic diversity were analyzed by per- forming a large number of experiments. The interaction mechanism was interpreted based on: i) retention characteristics of structurally related compounds, ii) retention modeling, iii) quantitative structure reten- tion relationship (QSRR), and iv) molecular docking. Small structural differences of related compounds (e.g., reflected in different lipophilicity and polarity) have been found to affect their different binding to human serum albumin. It was found that drug retention in HSA column can be successfully described by using the quadratic function. The isocratic (logk(14%)) and extrapolated (b0(LSS)) retention factors showed the highest correlation (r > 0.76) with the constant that defines the binding affinity for human serum albumin (ACD/I- Lab). Therefore, selected chromatographic parameters can demonstrate reliable applicability for rapid screening of drug-plasma protein binding in drug discovery. In QSRR study, the resulting SVM/logk(14%) and MLR/b0(LSS) models display high internal and external predictive power. The constitutional properties (double bonds, aromatic rings, benzyl, allyl, -amino and -sulfur containing functional groups) supported by the charged parts of surface area had a significant impact on human serum albumin-binding affinity, which was also confirmed with molecular docking study. The high structural diversity of the data set provides wide applicability of tested chromatographic conditions and constructed models for defining the phar- macokinetic profile and possible structural modifications that can increase plasma protein binding of newly synthesized, pharmaceutically important compounds.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches
VL  - 211
DO  - 10.1016/j.jpba.2022.114593
ER  - 

@article{
author = "Obradović, Darija and Radan, Milica and Đikić, Teodora and Popović-Nikolić, Marija and Oljačić, Slavica and Nikolić, Katarina",
year = "2022",
abstract = "The drug-human serum albumin binding interaction was evaluated on a stationary phase immobilized with human serum albumin using a mixture of phosphate buffer (pH 7.0) and acetonitrile modifier as mobile phase. The 33 compounds that have a wide structural and therapeutic diversity were analyzed by per- forming a large number of experiments. The interaction mechanism was interpreted based on: i) retention characteristics of structurally related compounds, ii) retention modeling, iii) quantitative structure reten- tion relationship (QSRR), and iv) molecular docking. Small structural differences of related compounds (e.g., reflected in different lipophilicity and polarity) have been found to affect their different binding to human serum albumin. It was found that drug retention in HSA column can be successfully described by using the quadratic function. The isocratic (logk(14%)) and extrapolated (b0(LSS)) retention factors showed the highest correlation (r > 0.76) with the constant that defines the binding affinity for human serum albumin (ACD/I- Lab). Therefore, selected chromatographic parameters can demonstrate reliable applicability for rapid screening of drug-plasma protein binding in drug discovery. In QSRR study, the resulting SVM/logk(14%) and MLR/b0(LSS) models display high internal and external predictive power. The constitutional properties (double bonds, aromatic rings, benzyl, allyl, -amino and -sulfur containing functional groups) supported by the charged parts of surface area had a significant impact on human serum albumin-binding affinity, which was also confirmed with molecular docking study. The high structural diversity of the data set provides wide applicability of tested chromatographic conditions and constructed models for defining the phar- macokinetic profile and possible structural modifications that can increase plasma protein binding of newly synthesized, pharmaceutically important compounds.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches",
volume = "211",
doi = "10.1016/j.jpba.2022.114593"
}

Obradović, D., Radan, M., Đikić, T., Popović-Nikolić, M., Oljačić, S.,& Nikolić, K.. (2022). The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 211.
https://doi.org/10.1016/j.jpba.2022.114593

Obradović D, Radan M, Đikić T, Popović-Nikolić M, Oljačić S, Nikolić K. The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches. in Journal of Pharmaceutical and Biomedical Analysis. 2022;211.
doi:10.1016/j.jpba.2022.114593 .

Obradović, Darija, Radan, Milica, Đikić, Teodora, Popović-Nikolić, Marija, Oljačić, Slavica, Nikolić, Katarina, "The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches" in Journal of Pharmaceutical and Biomedical Analysis, 211 (2022),
https://doi.org/10.1016/j.jpba.2022.114593 . .

TY  - JOUR
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Obradović, Darija
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3989
AB  - Permeability assessment of small molecules through the blood-brain barrier (BBB) plays a significant role in the development of effective central nervous system (CNS) drug candidates. Since in vivo methods for BBB permeability estimation require a lot of time and resources, in silico and in vitro approaches are becoming increasingly popular nowadays for faster and more economical predictions in early phases of drug discovery. In this work, through application of in vitro parallel artificial membrane permeability assay (PAMPA-BBB) and in silico computational methods we aimed to examine the passive permeability of eighteen compounds, which affect serotonin and dopamine levels in the CNS. The data set was consisted of novel six human dopamine transporter (hDAT) substrates that were previously identified as the most promising lead compounds for further optimisation to achieve neuroprotective effect, twelve approved CNS drugs, and their related compounds. Firstly, PAMPA methods was used to experimentally determine effective BBB permeability (Pe) for all studied compounds and obtained results were further submitted for quantitative structure permeability relationship (QSPR) analysis. QSPR models were built by using three different statistical methods: stepwise multiple linear regression (MLR), partial least square (PLS), and support-vector machine (SVM), while their predictive capability was tested through internal and external validation. Obtained statistical parameters (MLR- R2pred=-0.10; PLS- R2pred=0.64, r2m=0.69, r/2m=0.44; SVM- R2pred=0.57, r2m=0.72, r/2m=0.55) indicated that the SVM model is superior over others. The most important molecular descriptors (H0p and SolvEMt_3D) were identified and used to propose structural modifications of the examined compounds in order to improve their BBB permeability. Moreover, steered molecular dynamics (SMD) simulation was employed to comprehensively investigate the permeability pathway of compounds through a lipid bilayer. Taken together, the created QSPR model could be used as a reliable and fast pre-screening tool for BBB permeability prediction of structurally related CNS compounds, while performed MD simulations provide a good foundation for future in silico examination.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates
VL  - 168
DO  - 10.1016/j.ejps.2021.106056
ER  - 

@article{
author = "Radan, Milica and Đikić, Teodora and Obradović, Darija and Nikolić, Katarina",
year = "2022",
abstract = "Permeability assessment of small molecules through the blood-brain barrier (BBB) plays a significant role in the development of effective central nervous system (CNS) drug candidates. Since in vivo methods for BBB permeability estimation require a lot of time and resources, in silico and in vitro approaches are becoming increasingly popular nowadays for faster and more economical predictions in early phases of drug discovery. In this work, through application of in vitro parallel artificial membrane permeability assay (PAMPA-BBB) and in silico computational methods we aimed to examine the passive permeability of eighteen compounds, which affect serotonin and dopamine levels in the CNS. The data set was consisted of novel six human dopamine transporter (hDAT) substrates that were previously identified as the most promising lead compounds for further optimisation to achieve neuroprotective effect, twelve approved CNS drugs, and their related compounds. Firstly, PAMPA methods was used to experimentally determine effective BBB permeability (Pe) for all studied compounds and obtained results were further submitted for quantitative structure permeability relationship (QSPR) analysis. QSPR models were built by using three different statistical methods: stepwise multiple linear regression (MLR), partial least square (PLS), and support-vector machine (SVM), while their predictive capability was tested through internal and external validation. Obtained statistical parameters (MLR- R2pred=-0.10; PLS- R2pred=0.64, r2m=0.69, r/2m=0.44; SVM- R2pred=0.57, r2m=0.72, r/2m=0.55) indicated that the SVM model is superior over others. The most important molecular descriptors (H0p and SolvEMt_3D) were identified and used to propose structural modifications of the examined compounds in order to improve their BBB permeability. Moreover, steered molecular dynamics (SMD) simulation was employed to comprehensively investigate the permeability pathway of compounds through a lipid bilayer. Taken together, the created QSPR model could be used as a reliable and fast pre-screening tool for BBB permeability prediction of structurally related CNS compounds, while performed MD simulations provide a good foundation for future in silico examination.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates",
volume = "168",
doi = "10.1016/j.ejps.2021.106056"
}

Radan, M., Đikić, T., Obradović, D.,& Nikolić, K.. (2022). Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 168.
https://doi.org/10.1016/j.ejps.2021.106056

Radan M, Đikić T, Obradović D, Nikolić K. Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates. in European Journal of Pharmaceutical Sciences. 2022;168.
doi:10.1016/j.ejps.2021.106056 .

Radan, Milica, Đikić, Teodora, Obradović, Darija, Nikolić, Katarina, "Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates" in European Journal of Pharmaceutical Sciences, 168 (2022),
https://doi.org/10.1016/j.ejps.2021.106056 . .

TY  - CONF
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4738
PB  - European Research Network on Signal Transduction CA18133
C3  - 4GPCRnet Symposium
T1  - Application of computational methods in rational design of multi-target ligands as potential antipsychotics and antidepressants
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4738
ER  - 

@conference{
author = "Radan, Milica and Đikić, Teodora and Nikolić, Katarina",
year = "2022",
publisher = "European Research Network on Signal Transduction CA18133",
journal = "4GPCRnet Symposium",
title = "Application of computational methods in rational design of multi-target ligands as potential antipsychotics and antidepressants",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4738"
}

Radan, M., Đikić, T.,& Nikolić, K.. (2022). Application of computational methods in rational design of multi-target ligands as potential antipsychotics and antidepressants. in 4GPCRnet Symposium
European Research Network on Signal Transduction CA18133..
https://hdl.handle.net/21.15107/rcub_farfar_4738

Radan M, Đikić T, Nikolić K. Application of computational methods in rational design of multi-target ligands as potential antipsychotics and antidepressants. in 4GPCRnet Symposium. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4738 .

Radan, Milica, Đikić, Teodora, Nikolić, Katarina, "Application of computational methods in rational design of multi-target ligands as potential antipsychotics and antidepressants" in 4GPCRnet Symposium (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4738 .

TY  - CONF
AU  - Đoković, Nemanja
AU  - Ružić, Dušan
AU  - Đikić, Teodora
AU  - Cvijić, Sandra
AU  - Ignjatović, Jelisaveta
AU  - Ibrić, Svetlana
AU  - Baralić, Katarina
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4896
PB  - Hellenic Society of Medicinal Chemistry
C3  - 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium
T1  - Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4896
ER  - 

@conference{
author = "Đoković, Nemanja and Ružić, Dušan and Đikić, Teodora and Cvijić, Sandra and Ignjatović, Jelisaveta and Ibrić, Svetlana and Baralić, Katarina and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Nikolić, Katarina",
year = "2021",
publisher = "Hellenic Society of Medicinal Chemistry",
journal = "18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium",
title = "Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4896"
}

Đoković, N., Ružić, D., Đikić, T., Cvijić, S., Ignjatović, J., Ibrić, S., Baralić, K., Buha-Đorđević, A., Ćurčić, M., Đukić-Ćosić, D.,& Nikolić, K.. (2021). Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach. in 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium
Hellenic Society of Medicinal Chemistry..
https://hdl.handle.net/21.15107/rcub_farfar_4896

Đoković N, Ružić D, Đikić T, Cvijić S, Ignjatović J, Ibrić S, Baralić K, Buha-Đorđević A, Ćurčić M, Đukić-Ćosić D, Nikolić K. Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach. in 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_4896 .

Đoković, Nemanja, Ružić, Dušan, Đikić, Teodora, Cvijić, Sandra, Ignjatović, Jelisaveta, Ibrić, Svetlana, Baralić, Katarina, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Nikolić, Katarina, "Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach" in 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium (2021),
https://hdl.handle.net/21.15107/rcub_farfar_4896 .

TY  - JOUR
AU  - Đoković, Nemanja
AU  - Ružić, Dušan
AU  - Đikić, Teodora
AU  - Cvijić, Sandra
AU  - Ignjatović, Jelisaveta
AU  - Ibrić, Svetlana
AU  - Baralić, Katarina
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3830
AB  - Considering the urgent need for novel therapeutics in ongoing COVID-19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro). To screen FDA-approved drugs, we implemented structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data mining analysis of drug-gene-COVID-19 association. Through presented approach, we selected the most promising FDA approved drugs for further COVID-19 drug development campaigns and analysed them in context of available experimental data. To the best of our knowledge, this is unique in silico study which integrates structure-based molecular modeling of Mpro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.
PB  - John Wiley and Sons Inc
T2  - Molecular Informatics
T1  - An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease
VL  - 40
IS  - 5
DO  - 10.1002/minf.202000187
ER  - 

@article{
author = "Đoković, Nemanja and Ružić, Dušan and Đikić, Teodora and Cvijić, Sandra and Ignjatović, Jelisaveta and Ibrić, Svetlana and Baralić, Katarina and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Nikolić, Katarina",
year = "2021",
abstract = "Considering the urgent need for novel therapeutics in ongoing COVID-19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro). To screen FDA-approved drugs, we implemented structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data mining analysis of drug-gene-COVID-19 association. Through presented approach, we selected the most promising FDA approved drugs for further COVID-19 drug development campaigns and analysed them in context of available experimental data. To the best of our knowledge, this is unique in silico study which integrates structure-based molecular modeling of Mpro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.",
publisher = "John Wiley and Sons Inc",
journal = "Molecular Informatics",
title = "An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease",
volume = "40",
number = "5",
doi = "10.1002/minf.202000187"
}

Đoković, N., Ružić, D., Đikić, T., Cvijić, S., Ignjatović, J., Ibrić, S., Baralić, K., Buha-Đorđević, A., Ćurčić, M., Đukić-Ćosić, D.,& Nikolić, K.. (2021). An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease. in Molecular Informatics
John Wiley and Sons Inc., 40(5).
https://doi.org/10.1002/minf.202000187

Đoković N, Ružić D, Đikić T, Cvijić S, Ignjatović J, Ibrić S, Baralić K, Buha-Đorđević A, Ćurčić M, Đukić-Ćosić D, Nikolić K. An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease. in Molecular Informatics. 2021;40(5).
doi:10.1002/minf.202000187 .

Đoković, Nemanja, Ružić, Dušan, Đikić, Teodora, Cvijić, Sandra, Ignjatović, Jelisaveta, Ibrić, Svetlana, Baralić, Katarina, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Nikolić, Katarina, "An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease" in Molecular Informatics, 40, no. 5 (2021),
https://doi.org/10.1002/minf.202000187 . .

TY  - CONF
AU  - Radan, Milica
AU  - Ružić, Dušan
AU  - Antonijević, Mirjana
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4860
PB  - John Wiley & Sons Ltd.
C3  - Basic & Clinical Pharmacology & Toxicology (BCPT)
T1  - Application of Computational Methods for Antipsychotic Drug Design and Optimization
VL  - 128
IS  - S2
SP  - 3
EP  - 3
DO  - 10.1111/bcpt.13570
ER  - 

@conference{
author = "Radan, Milica and Ružić, Dušan and Antonijević, Mirjana and Đikić, Teodora and Nikolić, Katarina",
year = "2021",
publisher = "John Wiley & Sons Ltd.",
journal = "Basic & Clinical Pharmacology & Toxicology (BCPT)",
title = "Application of Computational Methods for Antipsychotic Drug Design and Optimization",
volume = "128",
number = "S2",
pages = "3-3",
doi = "10.1111/bcpt.13570"
}

Radan, M., Ružić, D., Antonijević, M., Đikić, T.,& Nikolić, K.. (2021). Application of Computational Methods for Antipsychotic Drug Design and Optimization. in Basic & Clinical Pharmacology & Toxicology (BCPT)
John Wiley & Sons Ltd.., 128(S2), 3-3.
https://doi.org/10.1111/bcpt.13570

Radan M, Ružić D, Antonijević M, Đikić T, Nikolić K. Application of Computational Methods for Antipsychotic Drug Design and Optimization. in Basic & Clinical Pharmacology & Toxicology (BCPT). 2021;128(S2):3-3.
doi:10.1111/bcpt.13570 .

Radan, Milica, Ružić, Dušan, Antonijević, Mirjana, Đikić, Teodora, Nikolić, Katarina, "Application of Computational Methods for Antipsychotic Drug Design and Optimization" in Basic & Clinical Pharmacology & Toxicology (BCPT), 128, no. S2 (2021):3-3,
https://doi.org/10.1111/bcpt.13570 . .

TY  - CONF
AU  - Radan, Milica
AU  - Ružić, Dušan
AU  - Antonijević, Milica
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4948
C3  - 4th ERNEST conference, virtual meeting, April 12-14, 2021, Poster Booklet.
T1  - Discovery of potential multi-target-directed 5-HT2A receptor ligands
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4948
ER  - 

@conference{
author = "Radan, Milica and Ružić, Dušan and Antonijević, Milica and Đikić, Teodora and Nikolić, Katarina",
year = "2021",
journal = "4th ERNEST conference, virtual meeting, April 12-14, 2021, Poster Booklet.",
title = "Discovery of potential multi-target-directed 5-HT2A receptor ligands",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4948"
}

Radan, M., Ružić, D., Antonijević, M., Đikić, T.,& Nikolić, K.. (2021). Discovery of potential multi-target-directed 5-HT2A receptor ligands. in 4th ERNEST conference, virtual meeting, April 12-14, 2021, Poster Booklet..
https://hdl.handle.net/21.15107/rcub_farfar_4948

Radan M, Ružić D, Antonijević M, Đikić T, Nikolić K. Discovery of potential multi-target-directed 5-HT2A receptor ligands. in 4th ERNEST conference, virtual meeting, April 12-14, 2021, Poster Booklet.. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_4948 .

Radan, Milica, Ružić, Dušan, Antonijević, Milica, Đikić, Teodora, Nikolić, Katarina, "Discovery of potential multi-target-directed 5-HT2A receptor ligands" in 4th ERNEST conference, virtual meeting, April 12-14, 2021, Poster Booklet. (2021),
https://hdl.handle.net/21.15107/rcub_farfar_4948 .

TY  - CONF
AU  - Senćanski, Milan
AU  - Glišić, S
AU  - Nikolić, Katarina
AU  - Đikić, Teodora
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4870
PB  - ADHER´N RISE CA18240
PB  - i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
C3  - 2nd General Meeting ADHER´N RISE CA18240, ONLINE EVENT, 15-16 July 2021
T1  - In silico drug repurposing of small organic molecules and peptide ligands for GPR56 receptor
SP  - 7
EP  - 7
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4870
ER  - 

@conference{
author = "Senćanski, Milan and Glišić, S and Nikolić, Katarina and Đikić, Teodora",
year = "2021",
publisher = "ADHER´N RISE CA18240, i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal",
journal = "2nd General Meeting ADHER´N RISE CA18240, ONLINE EVENT, 15-16 July 2021",
title = "In silico drug repurposing of small organic molecules and peptide ligands for GPR56 receptor",
pages = "7-7",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4870"
}

Senćanski, M., Glišić, S., Nikolić, K.,& Đikić, T.. (2021). In silico drug repurposing of small organic molecules and peptide ligands for GPR56 receptor. in 2nd General Meeting ADHER´N RISE CA18240, ONLINE EVENT, 15-16 July 2021
ADHER´N RISE CA18240., 7-7.
https://hdl.handle.net/21.15107/rcub_farfar_4870

Senćanski M, Glišić S, Nikolić K, Đikić T. In silico drug repurposing of small organic molecules and peptide ligands for GPR56 receptor. in 2nd General Meeting ADHER´N RISE CA18240, ONLINE EVENT, 15-16 July 2021. 2021;:7-7.
https://hdl.handle.net/21.15107/rcub_farfar_4870 .

Senćanski, Milan, Glišić, S, Nikolić, Katarina, Đikić, Teodora, "In silico drug repurposing of small organic molecules and peptide ligands for GPR56 receptor" in 2nd General Meeting ADHER´N RISE CA18240, ONLINE EVENT, 15-16 July 2021 (2021):7-7,
https://hdl.handle.net/21.15107/rcub_farfar_4870 .

TY  - CONF
AU  - Escolano, Carmen
AU  - Abas, Sonia
AU  - Rodriguez-Arevalo, Sergio
AU  - Bagan, Andrea
AU  - Griñan-Ferre, Christian
AU  - Vasilopoulou, Fotini
AU  - Pallas, Merce
AU  - Perez Lozano, Pilar
AU  - Brocos-Mosquera, Iria
AU  - Muguruza Carolina
AU  - Callado, Luis
AU  - Perez, Belen
AU  - Brea, Jose
AU  - Loza, M
AU  - Hernandez-Hernandez, Elena
AU  - Garcia-Sevilla, Jesus
AU  - Garcia-Fuster, M
AU  - Radan, Milica
AU  - Nikolić, Katarina
AU  - Đikić, Teodora
AU  - Diaz, Caridad
AU  - Jose Perez del Palacio
AU  - Ramos, Carmen
AU  - Vicente, Francisca
AU  - Molins, Elies
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4859
PB  - Wiley
C3  - The FASEB Journal
T1  - A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration
VL  - 35
IS  - S1
DO  - 10.1096/fasebj.2021.35.S1.04974
ER  - 

@conference{
author = "Escolano, Carmen and Abas, Sonia and Rodriguez-Arevalo, Sergio and Bagan, Andrea and Griñan-Ferre, Christian and Vasilopoulou, Fotini and Pallas, Merce and Perez Lozano, Pilar and Brocos-Mosquera, Iria and Muguruza Carolina and Callado, Luis and Perez, Belen and Brea, Jose and Loza, M and Hernandez-Hernandez, Elena and Garcia-Sevilla, Jesus and Garcia-Fuster, M and Radan, Milica and Nikolić, Katarina and Đikić, Teodora and Diaz, Caridad and Jose Perez del Palacio and Ramos, Carmen and Vicente, Francisca and Molins, Elies",
year = "2021",
publisher = "Wiley",
journal = "The FASEB Journal",
title = "A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration",
volume = "35",
number = "S1",
doi = "10.1096/fasebj.2021.35.S1.04974"
}

Escolano, C., Abas, S., Rodriguez-Arevalo, S., Bagan, A., Griñan-Ferre, C., Vasilopoulou, F., Pallas, M., Perez Lozano, P., Brocos-Mosquera, I., Muguruza Carolina, Callado, L., Perez, B., Brea, J., Loza, M., Hernandez-Hernandez, E., Garcia-Sevilla, J., Garcia-Fuster, M., Radan, M., Nikolić, K., Đikić, T., Diaz, C., Jose Perez del Palacio, Ramos, C., Vicente, F.,& Molins, E.. (2021). A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration. in The FASEB Journal
Wiley., 35(S1).
https://doi.org/10.1096/fasebj.2021.35.S1.04974

Escolano C, Abas S, Rodriguez-Arevalo S, Bagan A, Griñan-Ferre C, Vasilopoulou F, Pallas M, Perez Lozano P, Brocos-Mosquera I, Muguruza Carolina, Callado L, Perez B, Brea J, Loza M, Hernandez-Hernandez E, Garcia-Sevilla J, Garcia-Fuster M, Radan M, Nikolić K, Đikić T, Diaz C, Jose Perez del Palacio, Ramos C, Vicente F, Molins E. A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration. in The FASEB Journal. 2021;35(S1).
doi:10.1096/fasebj.2021.35.S1.04974 .

Escolano, Carmen, Abas, Sonia, Rodriguez-Arevalo, Sergio, Bagan, Andrea, Griñan-Ferre, Christian, Vasilopoulou, Fotini, Pallas, Merce, Perez Lozano, Pilar, Brocos-Mosquera, Iria, Muguruza Carolina, Callado, Luis, Perez, Belen, Brea, Jose, Loza, M, Hernandez-Hernandez, Elena, Garcia-Sevilla, Jesus, Garcia-Fuster, M, Radan, Milica, Nikolić, Katarina, Đikić, Teodora, Diaz, Caridad, Jose Perez del Palacio, Ramos, Carmen, Vicente, Francisca, Molins, Elies, "A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration" in The FASEB Journal, 35, no. S1 (2021),
https://doi.org/10.1096/fasebj.2021.35.S1.04974 . .

TY  - JOUR
AU  - Bon, Corentin
AU  - Si, Yang
AU  - Pernak, Melanie
AU  - Barbachowska, Magdalena
AU  - Levi-Acobas, Eva
AU  - Cadet Daniel, Veronique
AU  - Jallet, Corinne
AU  - Ružić, Dušan
AU  - Đoković, Nemanja
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
AU  - Halby, Ludovic
AU  - Arimondo, Paola B.
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3954
AB  - Histone methyltransferase DOT1L catalyzes mono-, di-and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.
PB  - MDPI
T2  - Molecules
T1  - Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein
VL  - 26
IS  - 17
DO  - 10.3390/molecules26175300
ER  - 

@article{
author = "Bon, Corentin and Si, Yang and Pernak, Melanie and Barbachowska, Magdalena and Levi-Acobas, Eva and Cadet Daniel, Veronique and Jallet, Corinne and Ružić, Dušan and Đoković, Nemanja and Đikić, Teodora and Nikolić, Katarina and Halby, Ludovic and Arimondo, Paola B.",
year = "2021",
abstract = "Histone methyltransferase DOT1L catalyzes mono-, di-and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.",
publisher = "MDPI",
journal = "Molecules",
title = "Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein",
volume = "26",
number = "17",
doi = "10.3390/molecules26175300"
}

Bon, C., Si, Y., Pernak, M., Barbachowska, M., Levi-Acobas, E., Cadet Daniel, V., Jallet, C., Ružić, D., Đoković, N., Đikić, T., Nikolić, K., Halby, L.,& Arimondo, P. B.. (2021). Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein. in Molecules
MDPI., 26(17).
https://doi.org/10.3390/molecules26175300

Bon C, Si Y, Pernak M, Barbachowska M, Levi-Acobas E, Cadet Daniel V, Jallet C, Ružić D, Đoković N, Đikić T, Nikolić K, Halby L, Arimondo PB. Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein. in Molecules. 2021;26(17).
doi:10.3390/molecules26175300 .

Bon, Corentin, Si, Yang, Pernak, Melanie, Barbachowska, Magdalena, Levi-Acobas, Eva, Cadet Daniel, Veronique, Jallet, Corinne, Ružić, Dušan, Đoković, Nemanja, Đikić, Teodora, Nikolić, Katarina, Halby, Ludovic, Arimondo, Paola B., "Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein" in Molecules, 26, no. 17 (2021),
https://doi.org/10.3390/molecules26175300 . .

TY  - CONF
AU  - Đikić, Teodora
AU  - Vučićević, Jelica
AU  - Laurila, Jonne
AU  - Radi, Marco
AU  - Veljković, Nevena
AU  - Xhaard, Henri
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4863
AB  - Centrally acting hypotensive imidazoline derivatives are agonists of α2-adrenoceptors and non-adrenergic
I1-imidazoline receptors. 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 cancer therapy. Never-
theless, rilmenidine itself does not represent a suitable candidate because of possible side effect caused by
activation of α 2 -adrenergic receptors. In our previous work, several novel rilmenidine-derived compounds
with anticancer potential and without an agonistic activity on α 2
-adrenoceptor were identified. Taking into
consideration that human α2
-adrenergic receptors belong to the rhodopsin-like class A of G protein-coupled
receptors (GPCRs), the biggest group of drug targets, that share structure similarity, it is reasonable to assume
that these ligands might have the affinity on some other receptors from the same class.
To investigate potential additional targets for novel imidazoline I1 agonists a reverse docking protocol on
107 GPCRs, using 63 imidazoline ligands and their 670 decoys was prepared. Unlike typical molecular dock-
ing protocol, where series of small molecules are docked in one macromolecular target, in case of reverse
docking a small-molecule is docked in the set of potential target proteins. Due to the availability of crystal
structures all of the included GPCRs, were in inactive state, and therefore suitable for identification of the
receptors antagonized by imidazoline ligands. Based on ROC curves and Enrichment Factors, 20 potential
off-target GPCRs were selected. To better assess the affinity of imidazoline derivatives for chosen receptors,
an additional docking study was performed, and docking scores of imidazolines were compared with docking
scores of known antagonists. Finally, to verify in silico results, three ligands with high scores and tree ligands
with low scores were tested for antagonistic activity on α2
-adrenergic receptors.
The protocol described here could be applied on all the small molecules, for the detection of potential inter-
actions with GPCRs of class A, in the early stage of drug design process. Additionally, this protocol is easily
expandable, by adding novel receptors/subfamily of receptors as soon as the crystal structures and/or 3D
models become available.
PB  - Department of Biology and Ecology Faculty of Sciences University of Novi Sad, Serbia
C3  - Biologia Serbica
T1  - Imidazolines: In silico off-target fishing in the class A of G protein-coupled receptors
VL  - 43
IS  - 1, Special Edition
SP  - 88
EP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4863
ER  - 

@conference{
author = "Đikić, Teodora and Vučićević, Jelica and Laurila, Jonne and Radi, Marco and Veljković, Nevena and Xhaard, Henri",
year = "2021",
abstract = "Centrally acting hypotensive imidazoline derivatives are agonists of α2-adrenoceptors and non-adrenergic
I1-imidazoline receptors. 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 cancer therapy. Never-
theless, rilmenidine itself does not represent a suitable candidate because of possible side effect caused by
activation of α 2 -adrenergic receptors. In our previous work, several novel rilmenidine-derived compounds
with anticancer potential and without an agonistic activity on α 2
-adrenoceptor were identified. Taking into
consideration that human α2
-adrenergic receptors belong to the rhodopsin-like class A of G protein-coupled
receptors (GPCRs), the biggest group of drug targets, that share structure similarity, it is reasonable to assume
that these ligands might have the affinity on some other receptors from the same class.
To investigate potential additional targets for novel imidazoline I1 agonists a reverse docking protocol on
107 GPCRs, using 63 imidazoline ligands and their 670 decoys was prepared. Unlike typical molecular dock-
ing protocol, where series of small molecules are docked in one macromolecular target, in case of reverse
docking a small-molecule is docked in the set of potential target proteins. Due to the availability of crystal
structures all of the included GPCRs, were in inactive state, and therefore suitable for identification of the
receptors antagonized by imidazoline ligands. Based on ROC curves and Enrichment Factors, 20 potential
off-target GPCRs were selected. To better assess the affinity of imidazoline derivatives for chosen receptors,
an additional docking study was performed, and docking scores of imidazolines were compared with docking
scores of known antagonists. Finally, to verify in silico results, three ligands with high scores and tree ligands
with low scores were tested for antagonistic activity on α2
-adrenergic receptors.
The protocol described here could be applied on all the small molecules, for the detection of potential inter-
actions with GPCRs of class A, in the early stage of drug design process. Additionally, this protocol is easily
expandable, by adding novel receptors/subfamily of receptors as soon as the crystal structures and/or 3D
models become available.",
publisher = "Department of Biology and Ecology Faculty of Sciences University of Novi Sad, Serbia",
journal = "Biologia Serbica",
title = "Imidazolines: In silico off-target fishing in the class A of G protein-coupled receptors",
volume = "43",
number = "1, Special Edition",
pages = "88-88",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4863"
}

Đikić, T., Vučićević, J., Laurila, J., Radi, M., Veljković, N.,& Xhaard, H.. (2021). Imidazolines: In silico off-target fishing in the class A of G protein-coupled receptors. in Biologia Serbica
Department of Biology and Ecology Faculty of Sciences University of Novi Sad, Serbia., 43(1, Special Edition), 88-88.
https://hdl.handle.net/21.15107/rcub_farfar_4863

Đikić T, Vučićević J, Laurila J, Radi M, Veljković N, Xhaard H. Imidazolines: In silico off-target fishing in the class A of G protein-coupled receptors. in Biologia Serbica. 2021;43(1, Special Edition):88-88.
https://hdl.handle.net/21.15107/rcub_farfar_4863 .

Đikić, Teodora, Vučićević, Jelica, Laurila, Jonne, Radi, Marco, Veljković, Nevena, Xhaard, Henri, "Imidazolines: In silico off-target fishing in the class A of G protein-coupled receptors" in Biologia Serbica, 43, no. 1, Special Edition (2021):88-88,
https://hdl.handle.net/21.15107/rcub_farfar_4863 .

TY  - CONF
AU  - Radan, Milica
AU  - Ružić, Dušan
AU  - Antonijević, Mirjana
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4856
PB  - EFMC-ISMC & EFMC-YMCS
C3  - EFMC-ISMC & EFMC-YMCS Virtual poster session Powered by the EFMC Young Scientists Network, September 9, 2020, Book of Abstracts
T1  - In silico rational druga design and modelling studies of novel 5-HT2A receptor antagonsts
SP  - 51
EP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4856
ER  - 

@conference{
author = "Radan, Milica and Ružić, Dušan and Antonijević, Mirjana and Đikić, Teodora and Nikolić, Katarina",
year = "2020",
publisher = "EFMC-ISMC & EFMC-YMCS",
journal = "EFMC-ISMC & EFMC-YMCS Virtual poster session Powered by the EFMC Young Scientists Network, September 9, 2020, Book of Abstracts",
title = "In silico rational druga design and modelling studies of novel 5-HT2A receptor antagonsts",
pages = "51-51",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4856"
}

Radan, M., Ružić, D., Antonijević, M., Đikić, T.,& Nikolić, K.. (2020). In silico rational druga design and modelling studies of novel 5-HT2A receptor antagonsts. in EFMC-ISMC & EFMC-YMCS Virtual poster session Powered by the EFMC Young Scientists Network, September 9, 2020, Book of Abstracts
EFMC-ISMC & EFMC-YMCS., 51-51.
https://hdl.handle.net/21.15107/rcub_farfar_4856

Radan M, Ružić D, Antonijević M, Đikić T, Nikolić K. In silico rational druga design and modelling studies of novel 5-HT2A receptor antagonsts. in EFMC-ISMC & EFMC-YMCS Virtual poster session Powered by the EFMC Young Scientists Network, September 9, 2020, Book of Abstracts. 2020;:51-51.
https://hdl.handle.net/21.15107/rcub_farfar_4856 .

Radan, Milica, Ružić, Dušan, Antonijević, Mirjana, Đikić, Teodora, Nikolić, Katarina, "In silico rational druga design and modelling studies of novel 5-HT2A receptor antagonsts" in EFMC-ISMC & EFMC-YMCS Virtual poster session Powered by the EFMC Young Scientists Network, September 9, 2020, Book of Abstracts (2020):51-51,
https://hdl.handle.net/21.15107/rcub_farfar_4856 .

TY  - JOUR
AU  - Gagić, Žarko
AU  - Ružić, Dušan
AU  - Đoković, Nemanja
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3502
AB  - Rational drug design implies usage of molecular modeling techniques such as pharmacophore modeling, molecular dynamics, virtual screening, and molecular docking to explain the activity of biomolecules, define molecular determinants for interaction with the drug target, and design more efficient drug candidates. Kinases play an essential role in cell function and therefore are extensively studied targets in drug design and discovery. Kinase inhibitors are clinically very important and widely used antineoplastic drugs. In this review, computational methods used in rational drug design of kinase inhibitors are discussed and compared, considering some representative case studies.
PB  - Frontiers Media S.A.
T2  - Frontiers in Chemistry
T1  - In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs
VL  - 7
DO  - 10.3389/fchem.2019.00873
ER  - 

@article{
author = "Gagić, Žarko and Ružić, Dušan and Đoković, Nemanja and Đikić, Teodora and Nikolić, Katarina",
year = "2020",
abstract = "Rational drug design implies usage of molecular modeling techniques such as pharmacophore modeling, molecular dynamics, virtual screening, and molecular docking to explain the activity of biomolecules, define molecular determinants for interaction with the drug target, and design more efficient drug candidates. Kinases play an essential role in cell function and therefore are extensively studied targets in drug design and discovery. Kinase inhibitors are clinically very important and widely used antineoplastic drugs. In this review, computational methods used in rational drug design of kinase inhibitors are discussed and compared, considering some representative case studies.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Chemistry",
title = "In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs",
volume = "7",
doi = "10.3389/fchem.2019.00873"
}

Gagić, Ž., Ružić, D., Đoković, N., Đikić, T.,& Nikolić, K.. (2020). In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs. in Frontiers in Chemistry
Frontiers Media S.A.., 7.
https://doi.org/10.3389/fchem.2019.00873

Gagić Ž, Ružić D, Đoković N, Đikić T, Nikolić K. In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs. in Frontiers in Chemistry. 2020;7.
doi:10.3389/fchem.2019.00873 .

Gagić, Žarko, Ružić, Dušan, Đoković, Nemanja, Đikić, Teodora, Nikolić, Katarina, "In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs" in Frontiers in Chemistry, 7 (2020),
https://doi.org/10.3389/fchem.2019.00873 . .

TY  - CONF
AU  - Radan, Milica
AU  - Ružić, Dušan
AU  - Antonijević, Mirjana
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4937
C3  - 10th International Conference on Biotechnology and Bioengineering (ICBB2020). Dec. 16-18, 2020. Virtual conference
T1  - Application of computational methods for antipsychotic drug design and optimization
SP  - 16
EP  - 16
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4937
ER  - 

@conference{
author = "Radan, Milica and Ružić, Dušan and Antonijević, Mirjana and Đikić, Teodora and Nikolić, Katarina",
year = "2020",
journal = "10th International Conference on Biotechnology and Bioengineering (ICBB2020). Dec. 16-18, 2020. Virtual conference",
title = "Application of computational methods for antipsychotic drug design and optimization",
pages = "16-16",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4937"
}

Radan, M., Ružić, D., Antonijević, M., Đikić, T.,& Nikolić, K.. (2020). Application of computational methods for antipsychotic drug design and optimization. in 10th International Conference on Biotechnology and Bioengineering (ICBB2020). Dec. 16-18, 2020. Virtual conference, 16-16.
https://hdl.handle.net/21.15107/rcub_farfar_4937

Radan M, Ružić D, Antonijević M, Đikić T, Nikolić K. Application of computational methods for antipsychotic drug design and optimization. in 10th International Conference on Biotechnology and Bioengineering (ICBB2020). Dec. 16-18, 2020. Virtual conference. 2020;:16-16.
https://hdl.handle.net/21.15107/rcub_farfar_4937 .

Radan, Milica, Ružić, Dušan, Antonijević, Mirjana, Đikić, Teodora, Nikolić, Katarina, "Application of computational methods for antipsychotic drug design and optimization" in 10th International Conference on Biotechnology and Bioengineering (ICBB2020). Dec. 16-18, 2020. Virtual conference (2020):16-16,
https://hdl.handle.net/21.15107/rcub_farfar_4937 .

TY  - CONF
AU  - Radan, Milica
AU  - Ružić, Dušan
AU  - Antonijević, Mirjana
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4873
PB  - European Research Network on Signal Transduction (ERNEST) CA18133
C3  - 3rd Meeting of the European Research Network on Signal Transduction (ERNEST COST Action CA18133), Signal transduction: From the genomic to the systems level (and everything in between), October 12-14, 2020, Abstract Booklet
T1  - Discovery of new 5-HT2A receptor antagonists with a strategy of combining ligand and target-based drug design methodologies
SP  - 75
EP  - 75
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4873
ER  - 

@conference{
author = "Radan, Milica and Ružić, Dušan and Antonijević, Mirjana and Đikić, Teodora and Nikolić, Katarina",
year = "2020",
publisher = "European Research Network on Signal Transduction (ERNEST) CA18133",
journal = "3rd Meeting of the European Research Network on Signal Transduction (ERNEST COST Action CA18133), Signal transduction: From the genomic to the systems level (and everything in between), October 12-14, 2020, Abstract Booklet",
title = "Discovery of new 5-HT2A receptor antagonists with a strategy of combining ligand and target-based drug design methodologies",
pages = "75-75",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4873"
}

Radan, M., Ružić, D., Antonijević, M., Đikić, T.,& Nikolić, K.. (2020). Discovery of new 5-HT2A receptor antagonists with a strategy of combining ligand and target-based drug design methodologies. in 3rd Meeting of the European Research Network on Signal Transduction (ERNEST COST Action CA18133), Signal transduction: From the genomic to the systems level (and everything in between), October 12-14, 2020, Abstract Booklet
European Research Network on Signal Transduction (ERNEST) CA18133., 75-75.
https://hdl.handle.net/21.15107/rcub_farfar_4873

Radan M, Ružić D, Antonijević M, Đikić T, Nikolić K. Discovery of new 5-HT2A receptor antagonists with a strategy of combining ligand and target-based drug design methodologies. in 3rd Meeting of the European Research Network on Signal Transduction (ERNEST COST Action CA18133), Signal transduction: From the genomic to the systems level (and everything in between), October 12-14, 2020, Abstract Booklet. 2020;:75-75.
https://hdl.handle.net/21.15107/rcub_farfar_4873 .

Radan, Milica, Ružić, Dušan, Antonijević, Mirjana, Đikić, Teodora, Nikolić, Katarina, "Discovery of new 5-HT2A receptor antagonists with a strategy of combining ligand and target-based drug design methodologies" in 3rd Meeting of the European Research Network on Signal Transduction (ERNEST COST Action CA18133), Signal transduction: From the genomic to the systems level (and everything in between), October 12-14, 2020, Abstract Booklet (2020):75-75,
https://hdl.handle.net/21.15107/rcub_farfar_4873 .

TY  - CONF
AU  - Radan, Milica
AU  - Ružić, Dušan
AU  - Antonijević, Mirjana
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4855
AB  - Serotonin 5-HT2A receptors (5-HT2AR) are highly expressed in human prefrontal cortex, essential for
learning and cognition [1]. Consequently, antagonists of these receptors are effective in treatment of
various neuropsychiatric disorders, such as depression, insomnia, schizophrenia, anxiety, and
cent progress in molecular modelling studies has led to significant success
in drug discovery using ligand and target-based methods. To design novel potent 5-HT2AR antagonists,
we report a strategy of combining three-dimensional quantitative structure-activity relationship (3DQSAR)
modelling with molecular docking and molecular dynamic (MD) simulation. Based on the
common structural features, data set of 75 compounds was divided into three clusters. Firstly, MD
simulations were carried out for each cluster representative in complex with 5-HT2AR, providing
important molecular level insight into their structure and dynamics. Afterward, to provide more
accurate information about binding modes in the active site of the receptor, obtained conformations
were used for docking studies and generation of the virtually bioactive conformations of all studied
ligands. In addition, 3D-QSAR study, utilizing selected conformers, was carried out to gain further
insights into the structural requirements that affect their antagonistic activity. Besides, some
commercially available 5-HT2AR antagonists were examined through in vitro PAMPA essay, as well as
in silico computational methods not only to improve BBB permeability of new designed compounds,
but also to establish promising tool to study their membrane permeability in detail. Overall, these and
future results will provide new methodologies that could be used as guidelines for rational drug design
of novel 5-HT2AR antagonists.
PB  - European Research Network on Signal Transduction (ERNEST) CA18133
C3  - 2nd ERNEST Online Meeting New Perspectives in Signal Transduction: GPCRs and Beyond, 28-30 March 2020, Abstract Book
T1  - Combined ligand-based and structure-based approaches in rational drug design of novel 5-HT2A receptor antagonists
SP  - 10
EP  - 10
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4855
ER  - 

@conference{
author = "Radan, Milica and Ružić, Dušan and Antonijević, Mirjana and Đikić, Teodora and Nikolić, Katarina",
year = "2020",
abstract = "Serotonin 5-HT2A receptors (5-HT2AR) are highly expressed in human prefrontal cortex, essential for
learning and cognition [1]. Consequently, antagonists of these receptors are effective in treatment of
various neuropsychiatric disorders, such as depression, insomnia, schizophrenia, anxiety, and
cent progress in molecular modelling studies has led to significant success
in drug discovery using ligand and target-based methods. To design novel potent 5-HT2AR antagonists,
we report a strategy of combining three-dimensional quantitative structure-activity relationship (3DQSAR)
modelling with molecular docking and molecular dynamic (MD) simulation. Based on the
common structural features, data set of 75 compounds was divided into three clusters. Firstly, MD
simulations were carried out for each cluster representative in complex with 5-HT2AR, providing
important molecular level insight into their structure and dynamics. Afterward, to provide more
accurate information about binding modes in the active site of the receptor, obtained conformations
were used for docking studies and generation of the virtually bioactive conformations of all studied
ligands. In addition, 3D-QSAR study, utilizing selected conformers, was carried out to gain further
insights into the structural requirements that affect their antagonistic activity. Besides, some
commercially available 5-HT2AR antagonists were examined through in vitro PAMPA essay, as well as
in silico computational methods not only to improve BBB permeability of new designed compounds,
but also to establish promising tool to study their membrane permeability in detail. Overall, these and
future results will provide new methodologies that could be used as guidelines for rational drug design
of novel 5-HT2AR antagonists.",
publisher = "European Research Network on Signal Transduction (ERNEST) CA18133",
journal = "2nd ERNEST Online Meeting New Perspectives in Signal Transduction: GPCRs and Beyond, 28-30 March 2020, Abstract Book",
title = "Combined ligand-based and structure-based approaches in rational drug design of novel 5-HT2A receptor antagonists",
pages = "10-10",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4855"
}

Radan, M., Ružić, D., Antonijević, M., Đikić, T.,& Nikolić, K.. (2020). Combined ligand-based and structure-based approaches in rational drug design of novel 5-HT2A receptor antagonists. in 2nd ERNEST Online Meeting New Perspectives in Signal Transduction: GPCRs and Beyond, 28-30 March 2020, Abstract Book
European Research Network on Signal Transduction (ERNEST) CA18133., 10-10.
https://hdl.handle.net/21.15107/rcub_farfar_4855

Radan M, Ružić D, Antonijević M, Đikić T, Nikolić K. Combined ligand-based and structure-based approaches in rational drug design of novel 5-HT2A receptor antagonists. in 2nd ERNEST Online Meeting New Perspectives in Signal Transduction: GPCRs and Beyond, 28-30 March 2020, Abstract Book. 2020;:10-10.
https://hdl.handle.net/21.15107/rcub_farfar_4855 .

Radan, Milica, Ružić, Dušan, Antonijević, Mirjana, Đikić, Teodora, Nikolić, Katarina, "Combined ligand-based and structure-based approaches in rational drug design of novel 5-HT2A receptor antagonists" in 2nd ERNEST Online Meeting New Perspectives in Signal Transduction: GPCRs and Beyond, 28-30 March 2020, Abstract Book (2020):10-10,
https://hdl.handle.net/21.15107/rcub_farfar_4855 .

TY  - JOUR
AU  - Abás, Sònia
AU  - Rodríguez-Arévalo, Sergio
AU  - Bagán, Andrea
AU  - Griñán-Ferré, Christian
AU  - Vasilopoulou, Foteini
AU  - Brocos-Mosquera, Iria
AU  - Muguruza, Carolina
AU  - Pérez, Belén
AU  - Molins, Elies
AU  - Luque, F. Javier
AU  - Pérez-Lozano, Pilar
AU  - De Jonghe, Steven
AU  - Daelemans, Dirk
AU  - Naesens, Lieve
AU  - Brea, José
AU  - Loza, M. Isabel
AU  - Hernández-Hernández, Elena
AU  - García-Sevilla, Jesús A.
AU  - García-Fuster, M. Julia
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
AU  - Pallàs, Mercè
AU  - Callado, Luis F.
AU  - Escolano, Carmen
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3768
AB  - Page 3630. The affiliation of the following authors needs to be corrected. Iria Brocos-Mosquera is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Carolina Muguruza is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Luis F. Callado is affiliated with Department of Pharmacology, University of the Basque Country, UPV/EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain.
PB  - American Chemical Society
T2  - Journal of Medicinal Chemistry
T1  - Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080)
VL  - 63
IS  - 18
SP  - 10529
DO  - 10.1021/acs.jmedchem.0c01324
ER  - 

@article{
author = "Abás, Sònia and Rodríguez-Arévalo, Sergio and Bagán, Andrea and Griñán-Ferré, Christian and Vasilopoulou, Foteini and Brocos-Mosquera, Iria and Muguruza, Carolina and Pérez, Belén and Molins, Elies and Luque, F. Javier and Pérez-Lozano, Pilar and De Jonghe, Steven and Daelemans, Dirk and Naesens, Lieve and Brea, José and Loza, M. Isabel and Hernández-Hernández, Elena and García-Sevilla, Jesús A. and García-Fuster, M. Julia and Radan, Milica and Đikić, Teodora and Nikolić, Katarina and Pallàs, Mercè and Callado, Luis F. and Escolano, Carmen",
year = "2020",
abstract = "Page 3630. The affiliation of the following authors needs to be corrected. Iria Brocos-Mosquera is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Carolina Muguruza is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Luis F. Callado is affiliated with Department of Pharmacology, University of the Basque Country, UPV/EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain.",
publisher = "American Chemical Society",
journal = "Journal of Medicinal Chemistry",
title = "Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080)",
volume = "63",
number = "18",
pages = "10529",
doi = "10.1021/acs.jmedchem.0c01324"
}

Abás, S., Rodríguez-Arévalo, S., Bagán, A., Griñán-Ferré, C., Vasilopoulou, F., Brocos-Mosquera, I., Muguruza, C., Pérez, B., Molins, E., Luque, F. J., Pérez-Lozano, P., De Jonghe, S., Daelemans, D., Naesens, L., Brea, J., Loza, M. I., Hernández-Hernández, E., García-Sevilla, J. A., García-Fuster, M. J., Radan, M., Đikić, T., Nikolić, K., Pallàs, M., Callado, L. F.,& Escolano, C.. (2020). Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080). in Journal of Medicinal Chemistry
American Chemical Society., 63(18), 10529.
https://doi.org/10.1021/acs.jmedchem.0c01324

Abás S, Rodríguez-Arévalo S, Bagán A, Griñán-Ferré C, Vasilopoulou F, Brocos-Mosquera I, Muguruza C, Pérez B, Molins E, Luque FJ, Pérez-Lozano P, De Jonghe S, Daelemans D, Naesens L, Brea J, Loza MI, Hernández-Hernández E, García-Sevilla JA, García-Fuster MJ, Radan M, Đikić T, Nikolić K, Pallàs M, Callado LF, Escolano C. Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080). in Journal of Medicinal Chemistry. 2020;63(18):10529.
doi:10.1021/acs.jmedchem.0c01324 .

Abás, Sònia, Rodríguez-Arévalo, Sergio, Bagán, Andrea, Griñán-Ferré, Christian, Vasilopoulou, Foteini, Brocos-Mosquera, Iria, Muguruza, Carolina, Pérez, Belén, Molins, Elies, Luque, F. Javier, Pérez-Lozano, Pilar, De Jonghe, Steven, Daelemans, Dirk, Naesens, Lieve, Brea, José, Loza, M. Isabel, Hernández-Hernández, Elena, García-Sevilla, Jesús A., García-Fuster, M. Julia, Radan, Milica, Đikić, Teodora, Nikolić, Katarina, Pallàs, Mercè, Callado, Luis F., Escolano, Carmen, "Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080)" in Journal of Medicinal Chemistry, 63, no. 18 (2020):10529,
https://doi.org/10.1021/acs.jmedchem.0c01324 . .

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  - JOUR
AU  - Abás, Sònia
AU  - Rodríguez-Arévalo, Sergio
AU  - Bagán, Andrea
AU  - Griñán-Ferré, Christian
AU  - Vasilopoulou, Foteini
AU  - Brocos-Mosquera, Iria
AU  - Muguruza, Carolina
AU  - Pérez, Belén
AU  - Molins, Elies
AU  - Luque, F. Javier
AU  - Pérez-Lozano, Pilar
AU  - De Jonghe, Steven
AU  - Daelemans, Dirk
AU  - Naesens, Lieve
AU  - Brea, José
AU  - Loza, M. Isabel
AU  - Hernández-Hernández, Elena
AU  - García-Sevilla, Jesús A.
AU  - García-Fuster, M. Julia
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Nikolić, Katarina
AU  - Pallàs, Mercè
AU  - Callado, Luis F.
AU  - Escolano, Carmen
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3576
AB  - Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore, bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions.
PB  - American Chemical Society
T2  - Journal of Medicinal Chemistry
T1  - Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease
VL  - 63
IS  - 7
SP  - 3610
EP  - 3633
DO  - 10.1021/acs.jmedchem.9b02080
ER  - 

@article{
author = "Abás, Sònia and Rodríguez-Arévalo, Sergio and Bagán, Andrea and Griñán-Ferré, Christian and Vasilopoulou, Foteini and Brocos-Mosquera, Iria and Muguruza, Carolina and Pérez, Belén and Molins, Elies and Luque, F. Javier and Pérez-Lozano, Pilar and De Jonghe, Steven and Daelemans, Dirk and Naesens, Lieve and Brea, José and Loza, M. Isabel and Hernández-Hernández, Elena and García-Sevilla, Jesús A. and García-Fuster, M. Julia and Radan, Milica and Đikić, Teodora and Nikolić, Katarina and Pallàs, Mercè and Callado, Luis F. and Escolano, Carmen",
year = "2020",
abstract = "Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore, bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions.",
publisher = "American Chemical Society",
journal = "Journal of Medicinal Chemistry",
title = "Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease",
volume = "63",
number = "7",
pages = "3610-3633",
doi = "10.1021/acs.jmedchem.9b02080"
}

Abás, S., Rodríguez-Arévalo, S., Bagán, A., Griñán-Ferré, C., Vasilopoulou, F., Brocos-Mosquera, I., Muguruza, C., Pérez, B., Molins, E., Luque, F. J., Pérez-Lozano, P., De Jonghe, S., Daelemans, D., Naesens, L., Brea, J., Loza, M. I., Hernández-Hernández, E., García-Sevilla, J. A., García-Fuster, M. J., Radan, M., Đikić, T., Nikolić, K., Pallàs, M., Callado, L. F.,& Escolano, C.. (2020). Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease. in Journal of Medicinal Chemistry
American Chemical Society., 63(7), 3610-3633.
https://doi.org/10.1021/acs.jmedchem.9b02080

Abás S, Rodríguez-Arévalo S, Bagán A, Griñán-Ferré C, Vasilopoulou F, Brocos-Mosquera I, Muguruza C, Pérez B, Molins E, Luque FJ, Pérez-Lozano P, De Jonghe S, Daelemans D, Naesens L, Brea J, Loza MI, Hernández-Hernández E, García-Sevilla JA, García-Fuster MJ, Radan M, Đikić T, Nikolić K, Pallàs M, Callado LF, Escolano C. Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease. in Journal of Medicinal Chemistry. 2020;63(7):3610-3633.
doi:10.1021/acs.jmedchem.9b02080 .

Abás, Sònia, Rodríguez-Arévalo, Sergio, Bagán, Andrea, Griñán-Ferré, Christian, Vasilopoulou, Foteini, Brocos-Mosquera, Iria, Muguruza, Carolina, Pérez, Belén, Molins, Elies, Luque, F. Javier, Pérez-Lozano, Pilar, De Jonghe, Steven, Daelemans, Dirk, Naesens, Lieve, Brea, José, Loza, M. Isabel, Hernández-Hernández, Elena, García-Sevilla, Jesús A., García-Fuster, M. Julia, Radan, Milica, Đikić, Teodora, Nikolić, Katarina, Pallàs, Mercè, Callado, Luis F., Escolano, Carmen, "Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease" in Journal of Medicinal Chemistry, 63, no. 7 (2020):3610-3633,
https://doi.org/10.1021/acs.jmedchem.9b02080 . .

TY  - CONF
AU  - Radan, Milica
AU  - Antonijević, Mirjana
AU  - Ružić, Dušan
AU  - Đikić, Teodora
AU  - Agbaba, Danica
AU  - Nikolić, Katarina
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4886
AB  - The serotonin 5-HT2A receptors are widely distributed throughout the central and the peripheral nervous system where they
play a key role in many physiological functions. Abnormal activity of 5-HT2A receptors is associated with various neurological
disorders, such as depression, schizophrenia, anxiety, and Parkinson disease. In order to analyze 3D-structure of the pharmacophore as well as binding kinetics of 5-HT2A-R antagonists, we have combined ligand and structure based approaches.
Three-dimensional quantitative structure-activity relationship (3D-QSAR) study in combination with molecular docking and
molecular dynamic (MD) simulation was used to identify key substituents responsible for high binding affinity and selectivity of
5-HT2A antagonists. The study was performed on wide range of structurally diverse antagonists that were divided into three
different clusters: clozapine, ziprasidone, and CHEMBL240876 derivates. We have obtained three different inactive, antagonistbound,
conformations of this receptor by using the 50ns long MD simulations with each cluster representative. Subsequently,
these conformations were used as templates for docking studies in order to find virtually bioactive conformations of ligands.
Selected virtually bioactive conformations were used for calculation of specific molecular descriptors (Grid Independent
Descriptors- GRIND) and 3D-QSAR model building. The 3D-QSAR approach was used to select the most influential variables
which were used for clarifying the structural features required for 5-HT2A antagonists. The reliability and predictive power of the
model was assessed using an external test set compounds and showed reasonable external predictability. The study provides
valuable information about the key structural features that are required in the rational drug design of novel 5-HT2A antagonists.
PB  - Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu
C3  - 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.
T1  - Structure and ligand based drug design strategies in the development of novel serotonin 5-HTt2a receptor antagonists
SP  - 14
EP  - 15
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4886
ER  - 

@conference{
author = "Radan, Milica and Antonijević, Mirjana and Ružić, Dušan and Đikić, Teodora and Agbaba, Danica and Nikolić, Katarina",
year = "2019",
abstract = "The serotonin 5-HT2A receptors are widely distributed throughout the central and the peripheral nervous system where they
play a key role in many physiological functions. Abnormal activity of 5-HT2A receptors is associated with various neurological
disorders, such as depression, schizophrenia, anxiety, and Parkinson disease. In order to analyze 3D-structure of the pharmacophore as well as binding kinetics of 5-HT2A-R antagonists, we have combined ligand and structure based approaches.
Three-dimensional quantitative structure-activity relationship (3D-QSAR) study in combination with molecular docking and
molecular dynamic (MD) simulation was used to identify key substituents responsible for high binding affinity and selectivity of
5-HT2A antagonists. The study was performed on wide range of structurally diverse antagonists that were divided into three
different clusters: clozapine, ziprasidone, and CHEMBL240876 derivates. We have obtained three different inactive, antagonistbound,
conformations of this receptor by using the 50ns long MD simulations with each cluster representative. Subsequently,
these conformations were used as templates for docking studies in order to find virtually bioactive conformations of ligands.
Selected virtually bioactive conformations were used for calculation of specific molecular descriptors (Grid Independent
Descriptors- GRIND) and 3D-QSAR model building. The 3D-QSAR approach was used to select the most influential variables
which were used for clarifying the structural features required for 5-HT2A antagonists. The reliability and predictive power of the
model was assessed using an external test set compounds and showed reasonable external predictability. The study provides
valuable information about the key structural features that are required in the rational drug design of novel 5-HT2A antagonists.",
publisher = "Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu",
journal = "2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.",
title = "Structure and ligand based drug design strategies in the development of novel serotonin 5-HTt2a receptor antagonists",
pages = "14-15",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4886"
}

Radan, M., Antonijević, M., Ružić, D., Đikić, T., Agbaba, D.,& Nikolić, K.. (2019). Structure and ligand based drug design strategies in the development of novel serotonin 5-HTt2a receptor antagonists. in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.
Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu., 14-15.
https://hdl.handle.net/21.15107/rcub_farfar_4886

Radan M, Antonijević M, Ružić D, Đikić T, Agbaba D, Nikolić K. Structure and ligand based drug design strategies in the development of novel serotonin 5-HTt2a receptor antagonists. in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.. 2019;:14-15.
https://hdl.handle.net/21.15107/rcub_farfar_4886 .

Radan, Milica, Antonijević, Mirjana, Ružić, Dušan, Đikić, Teodora, Agbaba, Danica, Nikolić, Katarina, "Structure and ligand based drug design strategies in the development of novel serotonin 5-HTt2a receptor antagonists" in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019. (2019):14-15,
https://hdl.handle.net/21.15107/rcub_farfar_4886 .

TY  - CONF
AU  - Đikić, Teodora
AU  - Martí, Yasmina
AU  - Spyrakis, Francesca
AU  - Lau, Thorsten
AU  - Benedetti, Paolo
AU  - Davey, Gavin
AU  - Schloss, Patrick
AU  - Yelekci, Kemal
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4887
AB  - Abnormally folded alpha-synuclein protein, dysfunctional mitochondria, increased oxidative stress and reduced dopamine
neurotransmitter synthesis are a
ll extremely well characterized phenomena in Parkinson’s disease (PD) and are thought to be interconnected. While direct
targeting of these areas has demonstrated neuroprotection in vitro and in vivo, there has been a major lack of success in clinical
trials. A critical component in the failure of these clinical trials is the inability to specifically target drugs to dopamine producing
neurons in the brain.
New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could
represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of
extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert
neuroprotective response because of their accumulation in the cytoplasm, are required.
By means of homology modeling, molecular docking and molecular dynamics simulations, we have generated 3D structure
models of hDAT in complex with substrate and inhibitors. Our results clearly reveal differences in binding kinetics of these
compounds to the hDAT in the open and closed conformations, critical for future drug design. The established in silico
approach allowed the identification of three promising substrate compounds that were subsequently analyzed for their
efficiency in inhibiting hDAT-dependent fluorescent substrate uptake, through in vitro live cell imaging experiments. Taken
together, our work presents the first implementation of a combined in silico/in vitro-approach enabling the selection of
promising dopaminergic neuron specific substrates.
PB  - Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu
C3  - 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.
T1  - In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease
SP  - 13
EP  - 14
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4887
ER  - 

@conference{
author = "Đikić, Teodora and Martí, Yasmina and Spyrakis, Francesca and Lau, Thorsten and Benedetti, Paolo and Davey, Gavin and Schloss, Patrick and Yelekci, Kemal",
year = "2019",
abstract = "Abnormally folded alpha-synuclein protein, dysfunctional mitochondria, increased oxidative stress and reduced dopamine
neurotransmitter synthesis are a
ll extremely well characterized phenomena in Parkinson’s disease (PD) and are thought to be interconnected. While direct
targeting of these areas has demonstrated neuroprotection in vitro and in vivo, there has been a major lack of success in clinical
trials. A critical component in the failure of these clinical trials is the inability to specifically target drugs to dopamine producing
neurons in the brain.
New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could
represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of
extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert
neuroprotective response because of their accumulation in the cytoplasm, are required.
By means of homology modeling, molecular docking and molecular dynamics simulations, we have generated 3D structure
models of hDAT in complex with substrate and inhibitors. Our results clearly reveal differences in binding kinetics of these
compounds to the hDAT in the open and closed conformations, critical for future drug design. The established in silico
approach allowed the identification of three promising substrate compounds that were subsequently analyzed for their
efficiency in inhibiting hDAT-dependent fluorescent substrate uptake, through in vitro live cell imaging experiments. Taken
together, our work presents the first implementation of a combined in silico/in vitro-approach enabling the selection of
promising dopaminergic neuron specific substrates.",
publisher = "Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu",
journal = "2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.",
title = "In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease",
pages = "13-14",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4887"
}

Đikić, T., Martí, Y., Spyrakis, F., Lau, T., Benedetti, P., Davey, G., Schloss, P.,& Yelekci, K.. (2019). In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease. in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.
Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu., 13-14.
https://hdl.handle.net/21.15107/rcub_farfar_4887

Đikić T, Martí Y, Spyrakis F, Lau T, Benedetti P, Davey G, Schloss P, Yelekci K. In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease. in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.. 2019;:13-14.
https://hdl.handle.net/21.15107/rcub_farfar_4887 .

Đikić, Teodora, Martí, Yasmina, Spyrakis, Francesca, Lau, Thorsten, Benedetti, Paolo, Davey, Gavin, Schloss, Patrick, Yelekci, Kemal, "In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease" in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019. (2019):13-14,
https://hdl.handle.net/21.15107/rcub_farfar_4887 .

TY  - CONF
AU  - Radan, Milica
AU  - Antonijević, Mirjana
AU  - Đikić, Teodora
AU  - Ružić, Dušan
AU  - Nikolić, Katarina
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4947
AB  - Serotonin 5-HT2A receptors are widely distributed in the human brain where they play a key role in
many physiological functions. Numerous neurological disorders caused by 5-HT2A malfunction have
made it a very attractive target. Therefore, analysis of 3D-structure of the pharmacophore as well as
binding kinetics of 5-HT2A antagonists would be beneficial for future rational drug design. Three dimensional quantitative structure-activity relationship (3D-QSAR) study was combined with molecular docking and molecular dynamic (MD) simulation in order to find crucial structural features responsible for high binding affinity and selectivity of 5-HT2A antagonists. This study was performed on wide range of structurally diverse antagonists that were divided into three different clusters: clozapine, ziprasidone, and CHEMBL240876 derivates. We have used 50ns MD simulations to obtain inactive, antagonist bound, conformations of each cluster representative. Subsequently, these conformations were used as templates for docking studies in order to find virtually bioactive conformations of examined compounds.
Selected virtually bioactive conformations were used for generation of specific molecular descriptors
(Grid Independent Descriptors- GRIND) and 3D-QSAR model building. The 3D-QSAR approach was used to identify the most important structural determinants responsible for the antagonistic activity and to propose structural modifications for novel antagonists of serotonin 5-HT2A receptors. Furthermore, diverse internal and external validation methods were applied. Obtained statistical parameters indicated the reliability and good predictive potential of the created model. Following these findings we have identified differences and similarities in the binding mode and pharmacophores of structurally diverse 5-HT2A antagonists as well as conformational changes they provoke.
PB  - University of Kragujevac, Kragujevac, Serbia
PB  - Bioengineering Reserach and
Development Centre BioIRC
C3  - ICCB 2019 Procedings - 8th International Conference on Computational Bioengineering, 4-6 September 2019, Belgrade, Serbia
T1  - Combined 3D-QSAR modeling, molecular dynamics and molecular docking studies in rational drug design of novel 5-HT2A antagonists
SP  - 84
EP  - 84
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4947
ER  - 

@conference{
author = "Radan, Milica and Antonijević, Mirjana and Đikić, Teodora and Ružić, Dušan and Nikolić, Katarina",
year = "2019",
abstract = "Serotonin 5-HT2A receptors are widely distributed in the human brain where they play a key role in
many physiological functions. Numerous neurological disorders caused by 5-HT2A malfunction have
made it a very attractive target. Therefore, analysis of 3D-structure of the pharmacophore as well as
binding kinetics of 5-HT2A antagonists would be beneficial for future rational drug design. Three dimensional quantitative structure-activity relationship (3D-QSAR) study was combined with molecular docking and molecular dynamic (MD) simulation in order to find crucial structural features responsible for high binding affinity and selectivity of 5-HT2A antagonists. This study was performed on wide range of structurally diverse antagonists that were divided into three different clusters: clozapine, ziprasidone, and CHEMBL240876 derivates. We have used 50ns MD simulations to obtain inactive, antagonist bound, conformations of each cluster representative. Subsequently, these conformations were used as templates for docking studies in order to find virtually bioactive conformations of examined compounds.
Selected virtually bioactive conformations were used for generation of specific molecular descriptors
(Grid Independent Descriptors- GRIND) and 3D-QSAR model building. The 3D-QSAR approach was used to identify the most important structural determinants responsible for the antagonistic activity and to propose structural modifications for novel antagonists of serotonin 5-HT2A receptors. Furthermore, diverse internal and external validation methods were applied. Obtained statistical parameters indicated the reliability and good predictive potential of the created model. Following these findings we have identified differences and similarities in the binding mode and pharmacophores of structurally diverse 5-HT2A antagonists as well as conformational changes they provoke.",
publisher = "University of Kragujevac, Kragujevac, Serbia, Bioengineering Reserach and
Development Centre BioIRC",
journal = "ICCB 2019 Procedings - 8th International Conference on Computational Bioengineering, 4-6 September 2019, Belgrade, Serbia",
title = "Combined 3D-QSAR modeling, molecular dynamics and molecular docking studies in rational drug design of novel 5-HT2A antagonists",
pages = "84-84",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4947"
}

Radan, M., Antonijević, M., Đikić, T., Ružić, D.,& Nikolić, K.. (2019). Combined 3D-QSAR modeling, molecular dynamics and molecular docking studies in rational drug design of novel 5-HT2A antagonists. in ICCB 2019 Procedings - 8th International Conference on Computational Bioengineering, 4-6 September 2019, Belgrade, Serbia
University of Kragujevac, Kragujevac, Serbia., 84-84.
https://hdl.handle.net/21.15107/rcub_farfar_4947

Radan M, Antonijević M, Đikić T, Ružić D, Nikolić K. Combined 3D-QSAR modeling, molecular dynamics and molecular docking studies in rational drug design of novel 5-HT2A antagonists. in ICCB 2019 Procedings - 8th International Conference on Computational Bioengineering, 4-6 September 2019, Belgrade, Serbia. 2019;:84-84.
https://hdl.handle.net/21.15107/rcub_farfar_4947 .

Radan, Milica, Antonijević, Mirjana, Đikić, Teodora, Ružić, Dušan, Nikolić, Katarina, "Combined 3D-QSAR modeling, molecular dynamics and molecular docking studies in rational drug design of novel 5-HT2A antagonists" in ICCB 2019 Procedings - 8th International Conference on Computational Bioengineering, 4-6 September 2019, Belgrade, Serbia (2019):84-84,
https://hdl.handle.net/21.15107/rcub_farfar_4947 .