TY  - CONF
AU  - Erić, Slavica
AU  - Hendricks, Charline
AU  - Zloh, Mire
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5012
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease, which treatment requires better understanding of underlying pathological processes. Epigenetic alterations as to some extent reversible processes might serve as another target for the therapy of MS for the aim of reprogramming inherited, environ-mentally initiated or by developing processes of MS influenced genotype and fenotype.
Cannabis sativa (CS) has been experimentally proven for positive outputs in treatment of MS, not just in elevating symptoms, but stopping the progress of disease. However, incidences of healing might focus further attention of wider impact of numerous constituents of CS that might play various roles in whole processes of possible healing, including epigenetic modulation. There are the proofs however that epigenetic changes are involved at certain stages of MS.
In this work, the potential of CS for treatment of altered epigenetic mechanisms involved in MS was investigated using network pharmacology methods. Constituents of CS were collected from literature, classified in few classes: cannabinoids, terpenoids, flavonoids, stilbenoids and alkaloids. Epigenetic targets (37) were chosen as overlap of predicted epigenetic targets for CS constituents by SwissTargetPrediction and EpigeneticTargetPro-filer, as well as epigenetic targets involved in MS obtained from GeneCArds and DisGeNet data bases. The relevance of chosen targets is supported in literature, as asscosiated with various processes of MS.
Network of CS constituents and chosen targets was mapped and analyzed by Cytoscape 3.9.1. Among the network consisted of 71 nodes and 266 edges, 266 interactions between CS constituents and epigenetic targets were indicated. The degree analysis of the obtained netwok was performed from the aspect of particular compound for possible targets and particular target for possible compounds interactions. Predictions of compunds and targets interactions are based on molecular similarity, therefore it remains to be further explored are those possible interactions associated with agonistic or antagonistic effects of the compounds. Promising results regarding possible interactions of CS constituents on epigenetic level of MS processes might be helpful for consideration of the therapy by this medical plant at various stages of MS development, taking into account other possible interactions with targets out of epigenetic landscape, associated with MS as well.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Computational study of interactions of Cannabis Sativa constituents with potential epigenetic targets involved in processes of multiple sclerosis
SP  - 44
EP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5012
ER  - 

@conference{
author = "Erić, Slavica and Hendricks, Charline and Zloh, Mire",
year = "2023",
abstract = "Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease, which treatment requires better understanding of underlying pathological processes. Epigenetic alterations as to some extent reversible processes might serve as another target for the therapy of MS for the aim of reprogramming inherited, environ-mentally initiated or by developing processes of MS influenced genotype and fenotype.
Cannabis sativa (CS) has been experimentally proven for positive outputs in treatment of MS, not just in elevating symptoms, but stopping the progress of disease. However, incidences of healing might focus further attention of wider impact of numerous constituents of CS that might play various roles in whole processes of possible healing, including epigenetic modulation. There are the proofs however that epigenetic changes are involved at certain stages of MS.
In this work, the potential of CS for treatment of altered epigenetic mechanisms involved in MS was investigated using network pharmacology methods. Constituents of CS were collected from literature, classified in few classes: cannabinoids, terpenoids, flavonoids, stilbenoids and alkaloids. Epigenetic targets (37) were chosen as overlap of predicted epigenetic targets for CS constituents by SwissTargetPrediction and EpigeneticTargetPro-filer, as well as epigenetic targets involved in MS obtained from GeneCArds and DisGeNet data bases. The relevance of chosen targets is supported in literature, as asscosiated with various processes of MS.
Network of CS constituents and chosen targets was mapped and analyzed by Cytoscape 3.9.1. Among the network consisted of 71 nodes and 266 edges, 266 interactions between CS constituents and epigenetic targets were indicated. The degree analysis of the obtained netwok was performed from the aspect of particular compound for possible targets and particular target for possible compounds interactions. Predictions of compunds and targets interactions are based on molecular similarity, therefore it remains to be further explored are those possible interactions associated with agonistic or antagonistic effects of the compounds. Promising results regarding possible interactions of CS constituents on epigenetic level of MS processes might be helpful for consideration of the therapy by this medical plant at various stages of MS development, taking into account other possible interactions with targets out of epigenetic landscape, associated with MS as well.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Computational study of interactions of Cannabis Sativa constituents with potential epigenetic targets involved in processes of multiple sclerosis",
pages = "44-44",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5012"
}

Erić, S., Hendricks, C.,& Zloh, M.. (2023). Computational study of interactions of Cannabis Sativa constituents with potential epigenetic targets involved in processes of multiple sclerosis. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 44-44.
https://hdl.handle.net/21.15107/rcub_farfar_5012

Erić S, Hendricks C, Zloh M. Computational study of interactions of Cannabis Sativa constituents with potential epigenetic targets involved in processes of multiple sclerosis. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:44-44.
https://hdl.handle.net/21.15107/rcub_farfar_5012 .

Erić, Slavica, Hendricks, Charline, Zloh, Mire, "Computational study of interactions of Cannabis Sativa constituents with potential epigenetic targets involved in processes of multiple sclerosis" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):44-44,
https://hdl.handle.net/21.15107/rcub_farfar_5012 .

TY  - CONF
AU  - Erić, Slavica
AU  - Vasilić, Đorđe
AU  - Ilić, Katarina
AU  - Zloh, Mire
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5011
AB  - The effects of Satureja Montana (SM) on retroviruses such as HIV-1 and SARS-CoV2, have been recorded in literature. Water-soluble phenols are confered as associated with inhibition of reverse transcriptases, whilst the potential oil constituents in treating viremias remains to be further explored. Investigation of some other Satureja spp. essential oils on HIV-1 and SARS-CoV2 viruses in vitro showed moderate inhibitory effects on its development. 
Screening of SM essential oil constituents on various targets was performed by SwissTarget Prediction program. Among 34 constituents in data set, 17 constituents showed certain probability of interaction with targets: 1-octen-3-ol, 2-hexenal, α-phellandrene, α-copaene, α-pinene, α-terpinene, α-terpinolene, α-tujene, aromadendren, β-myrcene, β-pinene, borneol, cis-ocimene, δ-cadinene, eugenol methylethar and γ-terpinene. Predicted interactions with targets include adenosine receptors 1, 2, and 3, as part of adenosine signaling, which modulation can help in adaptation and reduced damage due to cytokine storm associated with severe acute respiratory syndrome of corona virus type 2 (SARS CoV2). Accordingly, enhancing cellular ATP level can be benefitial for strengthening innate immune response against the virus. Regarding other targets predicted for interaction, possible following underlaying processes are included in effects of SM oil-soluble constituents: gland stimulation, transport enhancing, conjugation and subsequent elimination of foreign agents, hormone metabolism, up-regulation of host IER1α endoplasmatic reticulum stress response and interferon sygnaling pathways, transcription alterations, inhibition of cell proliferation, stabilization of DNA folding. The possible modulation of predicted CXC motif chemokine receptor type 3 (CXCR3) indicates possible role of SM constituents on T cell trafficking and function in identifying and destroying virus-infected cells. Recent findings provide the more detailed information about role of predicted carboanhidrase in biosynthesis processes, apart from known pH modulation, by equilibrating the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Synergistic action of medical plants constituents, as shown in case of SM, represent a sort of engineering, whilst detailed elucidation of particular molecular mechanisms involved in processes can help in precise indication, monitoring of pharmacological effects and improved application of possible therapy.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Investigation of molecular mechanism of action of Satureja Montana essential oil constituents related to effects on viremias
SP  - 43
EP  - 43
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5011
ER  - 

@conference{
author = "Erić, Slavica and Vasilić, Đorđe and Ilić, Katarina and Zloh, Mire",
year = "2023",
abstract = "The effects of Satureja Montana (SM) on retroviruses such as HIV-1 and SARS-CoV2, have been recorded in literature. Water-soluble phenols are confered as associated with inhibition of reverse transcriptases, whilst the potential oil constituents in treating viremias remains to be further explored. Investigation of some other Satureja spp. essential oils on HIV-1 and SARS-CoV2 viruses in vitro showed moderate inhibitory effects on its development. 
Screening of SM essential oil constituents on various targets was performed by SwissTarget Prediction program. Among 34 constituents in data set, 17 constituents showed certain probability of interaction with targets: 1-octen-3-ol, 2-hexenal, α-phellandrene, α-copaene, α-pinene, α-terpinene, α-terpinolene, α-tujene, aromadendren, β-myrcene, β-pinene, borneol, cis-ocimene, δ-cadinene, eugenol methylethar and γ-terpinene. Predicted interactions with targets include adenosine receptors 1, 2, and 3, as part of adenosine signaling, which modulation can help in adaptation and reduced damage due to cytokine storm associated with severe acute respiratory syndrome of corona virus type 2 (SARS CoV2). Accordingly, enhancing cellular ATP level can be benefitial for strengthening innate immune response against the virus. Regarding other targets predicted for interaction, possible following underlaying processes are included in effects of SM oil-soluble constituents: gland stimulation, transport enhancing, conjugation and subsequent elimination of foreign agents, hormone metabolism, up-regulation of host IER1α endoplasmatic reticulum stress response and interferon sygnaling pathways, transcription alterations, inhibition of cell proliferation, stabilization of DNA folding. The possible modulation of predicted CXC motif chemokine receptor type 3 (CXCR3) indicates possible role of SM constituents on T cell trafficking and function in identifying and destroying virus-infected cells. Recent findings provide the more detailed information about role of predicted carboanhidrase in biosynthesis processes, apart from known pH modulation, by equilibrating the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Synergistic action of medical plants constituents, as shown in case of SM, represent a sort of engineering, whilst detailed elucidation of particular molecular mechanisms involved in processes can help in precise indication, monitoring of pharmacological effects and improved application of possible therapy.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Investigation of molecular mechanism of action of Satureja Montana essential oil constituents related to effects on viremias",
pages = "43-43",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5011"
}

Erić, S., Vasilić, Đ., Ilić, K.,& Zloh, M.. (2023). Investigation of molecular mechanism of action of Satureja Montana essential oil constituents related to effects on viremias. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 43-43.
https://hdl.handle.net/21.15107/rcub_farfar_5011

Erić S, Vasilić Đ, Ilić K, Zloh M. Investigation of molecular mechanism of action of Satureja Montana essential oil constituents related to effects on viremias. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:43-43.
https://hdl.handle.net/21.15107/rcub_farfar_5011 .

Erić, Slavica, Vasilić, Đorđe, Ilić, Katarina, Zloh, Mire, "Investigation of molecular mechanism of action of Satureja Montana essential oil constituents related to effects on viremias" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):43-43,
https://hdl.handle.net/21.15107/rcub_farfar_5011 .

TY  - CONF
AU  - Erić, Slavica
AU  - Jović, Milena
AU  - Zloh, Mire
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5009
AB  - Echinacea spp. have long history of use, dating from American natives. Among ten, three species (Echinacea purpurea (L.), Echinacea pallida (Nutt.) and Echinacea angustifolia (DC.)), are the most used, alone or in mixes, for treatment of various conditions, such are infections, cancers etc. Recently, it was shown that Echinacea spp. are effective in treatment of COVID 19, inhibiting progress of SARS CoV2 development. Due to availability of structures of certain number of chemical constituents of Echinacea spp. and 3D structures of possible targets included in processes of interaction, elucidation of its molecular mechanisms of action was performed by computational methods.
Three approaches for evaluation of molecular mechanisms of Echinacea spp. constituents (24 from Echinacea purpurea and 10 from other Echinacea spp.) for possible treatment of recent COVID 19 pandemia are presented. First, docking studies of Echinacea spp. constituents (34) were performed on three targets, according to literature as the most important for SARS CoV2 virus spread and development: SARS CoV2 spike protein and angiotensin converting enzyme (ACE2) receptor responsible for virus entry, as well as SARS-CoV-2 metalloproteinase Mpro as the most responsible in mediation of viral transcription and replication. Second, physicochemical properties and pharmacokinetic-related characterization (Lipinksi Rule of five) of Echinacea spp. constituents in conformation with minimum energy, were performed by Data Warrior program. Results show that 4/34 compounds have negative values of log P (hydrophilic), 6/34 showed negative results regarding selection by Rule of five, among which 5 significantly differ in H-bonding capacity, which indicates different properties for oral absorption and distribution within the organism, as well as mode of action. Drug likeness, calculated for fragments of 34 constituents, is scattered within 15 units of difference. Third, the probability of interaction of Echinacea spp. constituents with targets was estimated by use of SwissTarget Prediction program, based on query molecule showing activity on certain class of targets. Results showed that cannabinoid receptors (CNR) 1 and 2 (17 and 16 units) and peroxisome proliferatoractivated receptor gamma (PPARγ) (15 units) are the most preferable targets for interactions. Possible molecular mechanisms involved in evidented pharmacological records in treatment of COVID 19 by Ehinacea spp. were elucidated with regard of results of all three methods.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods
SP  - 33
EP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5009
ER  - 

@conference{
author = "Erić, Slavica and Jović, Milena and Zloh, Mire",
year = "2023",
abstract = "Echinacea spp. have long history of use, dating from American natives. Among ten, three species (Echinacea purpurea (L.), Echinacea pallida (Nutt.) and Echinacea angustifolia (DC.)), are the most used, alone or in mixes, for treatment of various conditions, such are infections, cancers etc. Recently, it was shown that Echinacea spp. are effective in treatment of COVID 19, inhibiting progress of SARS CoV2 development. Due to availability of structures of certain number of chemical constituents of Echinacea spp. and 3D structures of possible targets included in processes of interaction, elucidation of its molecular mechanisms of action was performed by computational methods.
Three approaches for evaluation of molecular mechanisms of Echinacea spp. constituents (24 from Echinacea purpurea and 10 from other Echinacea spp.) for possible treatment of recent COVID 19 pandemia are presented. First, docking studies of Echinacea spp. constituents (34) were performed on three targets, according to literature as the most important for SARS CoV2 virus spread and development: SARS CoV2 spike protein and angiotensin converting enzyme (ACE2) receptor responsible for virus entry, as well as SARS-CoV-2 metalloproteinase Mpro as the most responsible in mediation of viral transcription and replication. Second, physicochemical properties and pharmacokinetic-related characterization (Lipinksi Rule of five) of Echinacea spp. constituents in conformation with minimum energy, were performed by Data Warrior program. Results show that 4/34 compounds have negative values of log P (hydrophilic), 6/34 showed negative results regarding selection by Rule of five, among which 5 significantly differ in H-bonding capacity, which indicates different properties for oral absorption and distribution within the organism, as well as mode of action. Drug likeness, calculated for fragments of 34 constituents, is scattered within 15 units of difference. Third, the probability of interaction of Echinacea spp. constituents with targets was estimated by use of SwissTarget Prediction program, based on query molecule showing activity on certain class of targets. Results showed that cannabinoid receptors (CNR) 1 and 2 (17 and 16 units) and peroxisome proliferatoractivated receptor gamma (PPARγ) (15 units) are the most preferable targets for interactions. Possible molecular mechanisms involved in evidented pharmacological records in treatment of COVID 19 by Ehinacea spp. were elucidated with regard of results of all three methods.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods",
pages = "33-33",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5009"
}

Erić, S., Jović, M.,& Zloh, M.. (2023). Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 33-33.
https://hdl.handle.net/21.15107/rcub_farfar_5009

Erić S, Jović M, Zloh M. Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:33-33.
https://hdl.handle.net/21.15107/rcub_farfar_5009 .

Erić, Slavica, Jović, Milena, Zloh, Mire, "Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):33-33,
https://hdl.handle.net/21.15107/rcub_farfar_5009 .

TY  - CONF
AU  - Antić, Natalija
AU  - Ilić, Milan
AU  - Marčetić, Mirjana
AU  - Drobac, Milica
AU  - Zloh, Mire
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5159
AB  - The Geronrum L. species have significant use in traditionaI medicine. Previous studies showed that these plants are rich in phytochemicals, especially in polyphenols and votatile compounds. The aim of this study was to determine potential target proteins for volatile compounds present in Geranium species and to provide a rationale for its current uses. The structures of identified volatile molecules were collated and their potential protein targets were predicted using PIDGIN software. The 2D and 3D structures of these compounds were generated using KingDraw software, while the 3D structures of selected target proteins
were obtained from Protein Data Bank. All volatile compounds were docked against the whole surface of endothelial PAS domain containing protein 1 (EPAS-1; PDBID: F310) and musarinic receptors M1 (PDBID:6WJC), M2 (PDBID:3UON), M4 (PDBID:5DG) and M5 (PDBID: 6OL9) using LeDock software. The study revealed several compounds with the potential to interact with target
proteins. Hexahydrofarnesyl acetone and γ-curcumene formed the most favorable binding poses inside the binding sites of all muscarinic receptors. Linalool and δ-guaiene forned favorable interactions to EPAS-l target protein. Predicted interaction energies are generally lower compared to ligands for these protein targts, mainly due to their size, hydrophobic properties, and the lack of H-bond forming groups. However, these compounds can fit the target site and form favorable interactions. It can be hypothesized that these plants and their extracts exert pharmacological activity via synergistic action of several components that
can interact with multiple proteins in vivo. Additionally, new therapeutic applications of these plants may be proposed based on the other targets predicted by PIDGIN but not reported in this abstract. Further in vitro studies are required to confirm in silico prediction and gain further insights on potential interactions of tested compounds and target proteins.
PB  - Sciforum
PB  - MDPI
C3  - 25th International Electronic Conference on Synthetic Organic Chemistry, 15–30 Nov 2021, online
T1  - In silico prediction of protein targets for volatile compounds of Geranium L. species
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5159
ER  - 

@conference{
author = "Antić, Natalija and Ilić, Milan and Marčetić, Mirjana and Drobac, Milica and Zloh, Mire",
year = "2021",
abstract = "The Geronrum L. species have significant use in traditionaI medicine. Previous studies showed that these plants are rich in phytochemicals, especially in polyphenols and votatile compounds. The aim of this study was to determine potential target proteins for volatile compounds present in Geranium species and to provide a rationale for its current uses. The structures of identified volatile molecules were collated and their potential protein targets were predicted using PIDGIN software. The 2D and 3D structures of these compounds were generated using KingDraw software, while the 3D structures of selected target proteins
were obtained from Protein Data Bank. All volatile compounds were docked against the whole surface of endothelial PAS domain containing protein 1 (EPAS-1; PDBID: F310) and musarinic receptors M1 (PDBID:6WJC), M2 (PDBID:3UON), M4 (PDBID:5DG) and M5 (PDBID: 6OL9) using LeDock software. The study revealed several compounds with the potential to interact with target
proteins. Hexahydrofarnesyl acetone and γ-curcumene formed the most favorable binding poses inside the binding sites of all muscarinic receptors. Linalool and δ-guaiene forned favorable interactions to EPAS-l target protein. Predicted interaction energies are generally lower compared to ligands for these protein targts, mainly due to their size, hydrophobic properties, and the lack of H-bond forming groups. However, these compounds can fit the target site and form favorable interactions. It can be hypothesized that these plants and their extracts exert pharmacological activity via synergistic action of several components that
can interact with multiple proteins in vivo. Additionally, new therapeutic applications of these plants may be proposed based on the other targets predicted by PIDGIN but not reported in this abstract. Further in vitro studies are required to confirm in silico prediction and gain further insights on potential interactions of tested compounds and target proteins.",
publisher = "Sciforum, MDPI",
journal = "25th International Electronic Conference on Synthetic Organic Chemistry, 15–30 Nov 2021, online",
title = "In silico prediction of protein targets for volatile compounds of Geranium L. species",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5159"
}

Antić, N., Ilić, M., Marčetić, M., Drobac, M.,& Zloh, M.. (2021). In silico prediction of protein targets for volatile compounds of Geranium L. species. in 25th International Electronic Conference on Synthetic Organic Chemistry, 15–30 Nov 2021, online
Sciforum..
https://hdl.handle.net/21.15107/rcub_farfar_5159

Antić N, Ilić M, Marčetić M, Drobac M, Zloh M. In silico prediction of protein targets for volatile compounds of Geranium L. species. in 25th International Electronic Conference on Synthetic Organic Chemistry, 15–30 Nov 2021, online. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_5159 .

Antić, Natalija, Ilić, Milan, Marčetić, Mirjana, Drobac, Milica, Zloh, Mire, "In silico prediction of protein targets for volatile compounds of Geranium L. species" in 25th International Electronic Conference on Synthetic Organic Chemistry, 15–30 Nov 2021, online (2021),
https://hdl.handle.net/21.15107/rcub_farfar_5159 .

TY  - JOUR
AU  - Erić, Slavica
AU  - Cvijetić, Ilija
AU  - Zloh, Mire
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3929
AB  - Metabolism of sulfur (sulfur assimilation pathway, SAP) is one of the key pathways for the pathogenesis and survival of persistant bacteria, such as Mycobacterium tuberculosis (Mtb), in the latent period. Adenosine 5'-phosphosulfate reductase (APSR) is an important enzyme involved in the SAP, absent from the human body, so it might represent a valid target for development of new antituberculosis drugs. This work aimed to develop 3D-QSAR model based on the crystal structure of APSR from Pseudomonas aeruginosa, which shows high degree of homology with APSR from Mtb, in complex with its substrate, adenosine 5'-phosphosulfate (APS). 3D-QSAR model was built from a set of 16 nucleotide analogues of APS using alignment-independent descriptors derived from molecular interaction fields (MIF). The model improves the understanding of the key characteristics of molecules necessary for the interaction with target, and enables the rational design of novel small molecule inhibitors of Mtb APSR.
AB  - Метаболизам  сумпора (пут асимилације  сумпора, SAP) један је од кључних путева  за  патогенезу  и  преживљавање  Mycobacterium  tuberculosis  (Mtb)  у  латентном  периоду.  Аденозин  5'-фосфосфат  редуктаза  (APSR)  је  значајан  ензим  који  је  укључен  у  SAP,  не  налази се у људском организму и може бити валиднo циљно место за развој нових анти- туберкулотика.  Циљ  овог  рада  је  развој  3D-QSAR  модела  који  се  заснива  на  кристалној  структури APSR из Pseudomonas aeruginosa, који има висок степен хомологије са APSR из  Mtb, у комплексу са супстратом, аденозин 5'-фосфoсулфатом (APS). 3D-QSAR модел је  постављен коришћењем сета 16 нуклеотидних аналога APS применом дескриптора неза- висних од полазних тачака, изведених из поља молекуларних интеракција (MIF). Модел  служи  за  боље  разумевање  кључних  карактеристика  молекула  неопходних  за  интерак- цију са циљним местом, у сврху рационалног дизајнирања малих молекула, инхибитора  APSR из Mtb.
PB  - Belgrade: Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - 3D-QSAR study of adenosine 5'-phosphosulfate (APS) analouges as ligands for APS reductase
T1  - 3D-QSAR студија аналога аденозин 5'-фосфосулфата (APS) као лиганда за APS редуктазу
VL  - 86
IS  - 6
SP  - 561
EP  - 570
DO  - 10.2298/JSC201128015E
ER  - 

@article{
author = "Erić, Slavica and Cvijetić, Ilija and Zloh, Mire",
year = "2021",
abstract = "Metabolism of sulfur (sulfur assimilation pathway, SAP) is one of the key pathways for the pathogenesis and survival of persistant bacteria, such as Mycobacterium tuberculosis (Mtb), in the latent period. Adenosine 5'-phosphosulfate reductase (APSR) is an important enzyme involved in the SAP, absent from the human body, so it might represent a valid target for development of new antituberculosis drugs. This work aimed to develop 3D-QSAR model based on the crystal structure of APSR from Pseudomonas aeruginosa, which shows high degree of homology with APSR from Mtb, in complex with its substrate, adenosine 5'-phosphosulfate (APS). 3D-QSAR model was built from a set of 16 nucleotide analogues of APS using alignment-independent descriptors derived from molecular interaction fields (MIF). The model improves the understanding of the key characteristics of molecules necessary for the interaction with target, and enables the rational design of novel small molecule inhibitors of Mtb APSR., Метаболизам  сумпора (пут асимилације  сумпора, SAP) један је од кључних путева  за  патогенезу  и  преживљавање  Mycobacterium  tuberculosis  (Mtb)  у  латентном  периоду.  Аденозин  5'-фосфосфат  редуктаза  (APSR)  је  значајан  ензим  који  је  укључен  у  SAP,  не  налази се у људском организму и може бити валиднo циљно место за развој нових анти- туберкулотика.  Циљ  овог  рада  је  развој  3D-QSAR  модела  који  се  заснива  на  кристалној  структури APSR из Pseudomonas aeruginosa, који има висок степен хомологије са APSR из  Mtb, у комплексу са супстратом, аденозин 5'-фосфoсулфатом (APS). 3D-QSAR модел је  постављен коришћењем сета 16 нуклеотидних аналога APS применом дескриптора неза- висних од полазних тачака, изведених из поља молекуларних интеракција (MIF). Модел  служи  за  боље  разумевање  кључних  карактеристика  молекула  неопходних  за  интерак- цију са циљним местом, у сврху рационалног дизајнирања малих молекула, инхибитора  APSR из Mtb.",
publisher = "Belgrade: Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "3D-QSAR study of adenosine 5'-phosphosulfate (APS) analouges as ligands for APS reductase, 3D-QSAR студија аналога аденозин 5'-фосфосулфата (APS) као лиганда за APS редуктазу",
volume = "86",
number = "6",
pages = "561-570",
doi = "10.2298/JSC201128015E"
}

Erić, S., Cvijetić, I.,& Zloh, M.. (2021). 3D-QSAR study of adenosine 5'-phosphosulfate (APS) analouges as ligands for APS reductase. in Journal of the Serbian Chemical Society
Belgrade: Serbian Chemical Society., 86(6), 561-570.
https://doi.org/10.2298/JSC201128015E

Erić S, Cvijetić I, Zloh M. 3D-QSAR study of adenosine 5'-phosphosulfate (APS) analouges as ligands for APS reductase. in Journal of the Serbian Chemical Society. 2021;86(6):561-570.
doi:10.2298/JSC201128015E .

Erić, Slavica, Cvijetić, Ilija, Zloh, Mire, "3D-QSAR study of adenosine 5'-phosphosulfate (APS) analouges as ligands for APS reductase" in Journal of the Serbian Chemical Society, 86, no. 6 (2021):561-570,
https://doi.org/10.2298/JSC201128015E . .

TY  - JOUR
AU  - Kozielewicz, Pawel
AU  - Paradowska, Katarzyna
AU  - Erić, Slavica
AU  - Wawer, Iwona
AU  - Zloh, Mire
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2192
AB  - Alkaloid-rich extract from Uncaria tomentosa (cat's claw) has been reported to cause apoptosis in cancer lines. Oxindole pentacyclic alkaloids of the plant are responsible for this effect, yet their biological mechanism of action is not fully understood. In this work the set of these alkaloids underwent an extensive theoretical study with reverse virtual screening and molecular docking methods implemented in AutoDock, AutoDock Vina, and Molegro Virtual Docker. The results from these computational methods indicate that inhibition of several important targets including dihydrofolate reductase and mouse double minute 2 homolog (MDM2) may be responsible for the biological activity of the alkaloids. The docking results also show that the alkaloids can interact with Dvl-2, Akt-2, and leukotriene A4 hydrolase. Reverse virtual screening and molecular docking are valuable tools to aid identification of protein targets for bioactive hit molecules and could guide the design of in-depth biochemical activity tests and utilization of these alkaloids in anticancer drug development. .
PB  - Springer Wien, Wien
T2  - Monatshefte für Chemie Chemical Monthly
T1  - Insights into mechanism of anticancer activity of pentacyclic oxindole alkaloids of Uncaria tomentosa by means of a computational reverse virtual screening and molecular docking approach
VL  - 145
IS  - 7
SP  - 1201
EP  - 1211
DO  - 10.1007/s00706-014-1212-y
ER  - 

@article{
author = "Kozielewicz, Pawel and Paradowska, Katarzyna and Erić, Slavica and Wawer, Iwona and Zloh, Mire",
year = "2014",
abstract = "Alkaloid-rich extract from Uncaria tomentosa (cat's claw) has been reported to cause apoptosis in cancer lines. Oxindole pentacyclic alkaloids of the plant are responsible for this effect, yet their biological mechanism of action is not fully understood. In this work the set of these alkaloids underwent an extensive theoretical study with reverse virtual screening and molecular docking methods implemented in AutoDock, AutoDock Vina, and Molegro Virtual Docker. The results from these computational methods indicate that inhibition of several important targets including dihydrofolate reductase and mouse double minute 2 homolog (MDM2) may be responsible for the biological activity of the alkaloids. The docking results also show that the alkaloids can interact with Dvl-2, Akt-2, and leukotriene A4 hydrolase. Reverse virtual screening and molecular docking are valuable tools to aid identification of protein targets for bioactive hit molecules and could guide the design of in-depth biochemical activity tests and utilization of these alkaloids in anticancer drug development. .",
publisher = "Springer Wien, Wien",
journal = "Monatshefte für Chemie Chemical Monthly",
title = "Insights into mechanism of anticancer activity of pentacyclic oxindole alkaloids of Uncaria tomentosa by means of a computational reverse virtual screening and molecular docking approach",
volume = "145",
number = "7",
pages = "1201-1211",
doi = "10.1007/s00706-014-1212-y"
}

Kozielewicz, P., Paradowska, K., Erić, S., Wawer, I.,& Zloh, M.. (2014). Insights into mechanism of anticancer activity of pentacyclic oxindole alkaloids of Uncaria tomentosa by means of a computational reverse virtual screening and molecular docking approach. in Monatshefte für Chemie Chemical Monthly
Springer Wien, Wien., 145(7), 1201-1211.
https://doi.org/10.1007/s00706-014-1212-y

Kozielewicz P, Paradowska K, Erić S, Wawer I, Zloh M. Insights into mechanism of anticancer activity of pentacyclic oxindole alkaloids of Uncaria tomentosa by means of a computational reverse virtual screening and molecular docking approach. in Monatshefte für Chemie Chemical Monthly. 2014;145(7):1201-1211.
doi:10.1007/s00706-014-1212-y .

Kozielewicz, Pawel, Paradowska, Katarzyna, Erić, Slavica, Wawer, Iwona, Zloh, Mire, "Insights into mechanism of anticancer activity of pentacyclic oxindole alkaloids of Uncaria tomentosa by means of a computational reverse virtual screening and molecular docking approach" in Monatshefte für Chemie Chemical Monthly, 145, no. 7 (2014):1201-1211,
https://doi.org/10.1007/s00706-014-1212-y . .

TY  - JOUR
AU  - Kalinić, Marko
AU  - Zloh, Mire
AU  - Erić, Slavica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2140
AB  - Enhancer of Zeste Homolog 2 (EZH2) is a SET domain protein lysine methyltransferase (PKMT) which has recently emerged as a chemically tractable and therapeutically promising epigenetic target, evidenced by the discovery and characterization of potent and highly selective EZH2 inhibitors. However, no experimental structures of the inhibitors co-crystallized to EZH2 have been resolved, and the structural basis for their activity and selectivity remains unknown. Considering the need to minimize cross-reactivity between prospective PKMT inhibitors, much can be learned from understanding the molecular basis for selective inhibition of EZH2. Thus, to elucidate the binding of small-molecule inhibitors to EZH2, we have developed a model of its fully-formed cofactor binding site and used it to carry out molecular dynamics simulations of protein-ligand complexes, followed by molecular mechanics/generalized born surface area calculations. The obtained results are in good agreement with biochemical inhibition data and reflect the structure-activity relationships of known ligands. Our findings suggest that the variable and flexible post-SET domain plays an important role in inhibitor binding, allowing possibly distinct binding modes of inhibitors with only small variations in their structure. Insights from this study present a good basis for design of novel and optimization of existing compounds targeting the cofactor binding site of EZH2.
PB  - Springer, Dordrecht
T2  - Journal of Computer-Aided Molecular Design
T1  - Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2
VL  - 28
IS  - 11
SP  - 1109
EP  - 1128
DO  - 10.1007/s10822-014-9788-1
ER  - 

@article{
author = "Kalinić, Marko and Zloh, Mire and Erić, Slavica",
year = "2014",
abstract = "Enhancer of Zeste Homolog 2 (EZH2) is a SET domain protein lysine methyltransferase (PKMT) which has recently emerged as a chemically tractable and therapeutically promising epigenetic target, evidenced by the discovery and characterization of potent and highly selective EZH2 inhibitors. However, no experimental structures of the inhibitors co-crystallized to EZH2 have been resolved, and the structural basis for their activity and selectivity remains unknown. Considering the need to minimize cross-reactivity between prospective PKMT inhibitors, much can be learned from understanding the molecular basis for selective inhibition of EZH2. Thus, to elucidate the binding of small-molecule inhibitors to EZH2, we have developed a model of its fully-formed cofactor binding site and used it to carry out molecular dynamics simulations of protein-ligand complexes, followed by molecular mechanics/generalized born surface area calculations. The obtained results are in good agreement with biochemical inhibition data and reflect the structure-activity relationships of known ligands. Our findings suggest that the variable and flexible post-SET domain plays an important role in inhibitor binding, allowing possibly distinct binding modes of inhibitors with only small variations in their structure. Insights from this study present a good basis for design of novel and optimization of existing compounds targeting the cofactor binding site of EZH2.",
publisher = "Springer, Dordrecht",
journal = "Journal of Computer-Aided Molecular Design",
title = "Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2",
volume = "28",
number = "11",
pages = "1109-1128",
doi = "10.1007/s10822-014-9788-1"
}

Kalinić, M., Zloh, M.,& Erić, S.. (2014). Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2. in Journal of Computer-Aided Molecular Design
Springer, Dordrecht., 28(11), 1109-1128.
https://doi.org/10.1007/s10822-014-9788-1

Kalinić M, Zloh M, Erić S. Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2. in Journal of Computer-Aided Molecular Design. 2014;28(11):1109-1128.
doi:10.1007/s10822-014-9788-1 .

Kalinić, Marko, Zloh, Mire, Erić, Slavica, "Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2" in Journal of Computer-Aided Molecular Design, 28, no. 11 (2014):1109-1128,
https://doi.org/10.1007/s10822-014-9788-1 . .

TY  - JOUR
AU  - Erić, Slavica
AU  - Kalinić, Marko
AU  - Ilić, K.
AU  - Zloh, Mire
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2133
AB  - P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are two members of the adenosine triphosphate (ATP) binding cassette (ABC) family of transporters which function as membrane efflux transporters and display considerable substrate promiscuity. Both are known to significantly influence the absorption, distribution and elimination of drugs, mediate drug-drug interactions and contribute to multiple drug resistance (MDR) of cancer cells. Correspondingly, timely characterization of the interaction of novel leads and drug candidates with these two transporters is of great importance. In this study, several computational classification models for prediction of transport and inhibition of P-gp and BCRP, respectively, were developed based on newly compiled and critically evaluated experimental data. Artificial neural network (ANN) and support vector machine (SVM) ensemble based models were explored, as well as knowledge-based approaches to descriptor selection. The average overall classification accuracy of best performing models was 82% for P-gp transport, 88% for BCRP transport, 89% for P-gp inhibition and 87% for BCRP inhibition, determined across an array of different test sets. An analysis of substrate overlap between P-gp and BCRP was also performed. The accuracy, simplicity and interpretability of the proposed models suggest that they could be of significant utility in the drug discovery and development settings.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Saudi Pharmaceutical Journal
T1  - Computational classification models for predicting the interaction of drugs with P-glycoprotein and breast cancer resistance protein
VL  - 25
IS  - 12
SP  - 955
EP  - 982
DO  - 10.1080/1062936X.2014.976265
ER  - 

@article{
author = "Erić, Slavica and Kalinić, Marko and Ilić, K. and Zloh, Mire",
year = "2014",
abstract = "P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are two members of the adenosine triphosphate (ATP) binding cassette (ABC) family of transporters which function as membrane efflux transporters and display considerable substrate promiscuity. Both are known to significantly influence the absorption, distribution and elimination of drugs, mediate drug-drug interactions and contribute to multiple drug resistance (MDR) of cancer cells. Correspondingly, timely characterization of the interaction of novel leads and drug candidates with these two transporters is of great importance. In this study, several computational classification models for prediction of transport and inhibition of P-gp and BCRP, respectively, were developed based on newly compiled and critically evaluated experimental data. Artificial neural network (ANN) and support vector machine (SVM) ensemble based models were explored, as well as knowledge-based approaches to descriptor selection. The average overall classification accuracy of best performing models was 82% for P-gp transport, 88% for BCRP transport, 89% for P-gp inhibition and 87% for BCRP inhibition, determined across an array of different test sets. An analysis of substrate overlap between P-gp and BCRP was also performed. The accuracy, simplicity and interpretability of the proposed models suggest that they could be of significant utility in the drug discovery and development settings.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Saudi Pharmaceutical Journal",
title = "Computational classification models for predicting the interaction of drugs with P-glycoprotein and breast cancer resistance protein",
volume = "25",
number = "12",
pages = "955-982",
doi = "10.1080/1062936X.2014.976265"
}

Erić, S., Kalinić, M., Ilić, K.,& Zloh, M.. (2014). Computational classification models for predicting the interaction of drugs with P-glycoprotein and breast cancer resistance protein. in Saudi Pharmaceutical Journal
Taylor & Francis Ltd, Abingdon., 25(12), 955-982.
https://doi.org/10.1080/1062936X.2014.976265

Erić S, Kalinić M, Ilić K, Zloh M. Computational classification models for predicting the interaction of drugs with P-glycoprotein and breast cancer resistance protein. in Saudi Pharmaceutical Journal. 2014;25(12):955-982.
doi:10.1080/1062936X.2014.976265 .

Erić, Slavica, Kalinić, Marko, Ilić, K., Zloh, Mire, "Computational classification models for predicting the interaction of drugs with P-glycoprotein and breast cancer resistance protein" in Saudi Pharmaceutical Journal, 25, no. 12 (2014):955-982,
https://doi.org/10.1080/1062936X.2014.976265 . .

TY  - JOUR
AU  - Erić, Slavica
AU  - Solmajer, Tom
AU  - Kotnik, Miha
AU  - Zloh, Mire
AU  - Agbaba, Danica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1984
AB  - Modeling of alpha(1a), alpha(1b), and alpha(1d) adrenergic receptor subtypes has been performed using InsightII software and bovine rhodopsin as a template. Adrenaline and noradrenaline, as endogenous agonists, were docked to validate the developed models, explore the putative binding sites, and calculate relative docking scores. alpha(1)-Adrenergic antagonists with the highest order of selectivity and activity at specific receptor subtypes were then chosen for docking into the corresponding receptor models. Docking simulations were performed using the FlexX module implemented in the Sybil program. PMF scoring functions of the obtained complexes calculated as relative to PMF scoring functions for noradrenaline-receptor subtype complexes were then used for correlation with selectivity on different alpha(1)-adrenergic subtypes. Good correlations were obtained for most receptor subtype-selectivity pairs: (1) using PMF scores calculated for ligands in complex with alpha(1a)-receptor subtype, r = 0.7503 for alpha(1a/1b) and r = 0.6336 for alpha(1a/1d) selectivity; (2) using PMF scores calculated for ligands in complex with alpha(1b) receptor subtype, r = 0.7632 for alpha(1a/1b) and r = 0.7061 for alpha(1b/1d) selectivity; (3) using PMF scores for ligands in complex with alpha(1d) receptor subtype, r = 0.7377 for alpha(1a/1d) and r = 0.9913 for alpha(1b/1d) selectivity.
PB  - Springer Wien, Wien
T2  - Monatshefte für Chemie Chemical Monthly
T1  - Study of the selectivity of alpha(1)-adrenergic antagonists by molecular modeling of alpha(1a)-, alpha(1b)-, and alpha(1d)-adrenergic receptor subtypes and docking simulations
VL  - 144
IS  - 6
SP  - 903
EP  - 912
DO  - 10.1007/s00706-013-0966-y
ER  - 

@article{
author = "Erić, Slavica and Solmajer, Tom and Kotnik, Miha and Zloh, Mire and Agbaba, Danica",
year = "2013",
abstract = "Modeling of alpha(1a), alpha(1b), and alpha(1d) adrenergic receptor subtypes has been performed using InsightII software and bovine rhodopsin as a template. Adrenaline and noradrenaline, as endogenous agonists, were docked to validate the developed models, explore the putative binding sites, and calculate relative docking scores. alpha(1)-Adrenergic antagonists with the highest order of selectivity and activity at specific receptor subtypes were then chosen for docking into the corresponding receptor models. Docking simulations were performed using the FlexX module implemented in the Sybil program. PMF scoring functions of the obtained complexes calculated as relative to PMF scoring functions for noradrenaline-receptor subtype complexes were then used for correlation with selectivity on different alpha(1)-adrenergic subtypes. Good correlations were obtained for most receptor subtype-selectivity pairs: (1) using PMF scores calculated for ligands in complex with alpha(1a)-receptor subtype, r = 0.7503 for alpha(1a/1b) and r = 0.6336 for alpha(1a/1d) selectivity; (2) using PMF scores calculated for ligands in complex with alpha(1b) receptor subtype, r = 0.7632 for alpha(1a/1b) and r = 0.7061 for alpha(1b/1d) selectivity; (3) using PMF scores for ligands in complex with alpha(1d) receptor subtype, r = 0.7377 for alpha(1a/1d) and r = 0.9913 for alpha(1b/1d) selectivity.",
publisher = "Springer Wien, Wien",
journal = "Monatshefte für Chemie Chemical Monthly",
title = "Study of the selectivity of alpha(1)-adrenergic antagonists by molecular modeling of alpha(1a)-, alpha(1b)-, and alpha(1d)-adrenergic receptor subtypes and docking simulations",
volume = "144",
number = "6",
pages = "903-912",
doi = "10.1007/s00706-013-0966-y"
}

Erić, S., Solmajer, T., Kotnik, M., Zloh, M.,& Agbaba, D.. (2013). Study of the selectivity of alpha(1)-adrenergic antagonists by molecular modeling of alpha(1a)-, alpha(1b)-, and alpha(1d)-adrenergic receptor subtypes and docking simulations. in Monatshefte für Chemie Chemical Monthly
Springer Wien, Wien., 144(6), 903-912.
https://doi.org/10.1007/s00706-013-0966-y

Erić S, Solmajer T, Kotnik M, Zloh M, Agbaba D. Study of the selectivity of alpha(1)-adrenergic antagonists by molecular modeling of alpha(1a)-, alpha(1b)-, and alpha(1d)-adrenergic receptor subtypes and docking simulations. in Monatshefte für Chemie Chemical Monthly. 2013;144(6):903-912.
doi:10.1007/s00706-013-0966-y .

Erić, Slavica, Solmajer, Tom, Kotnik, Miha, Zloh, Mire, Agbaba, Danica, "Study of the selectivity of alpha(1)-adrenergic antagonists by molecular modeling of alpha(1a)-, alpha(1b)-, and alpha(1d)-adrenergic receptor subtypes and docking simulations" in Monatshefte für Chemie Chemical Monthly, 144, no. 6 (2013):903-912,
https://doi.org/10.1007/s00706-013-0966-y . .

TY  - JOUR
AU  - Erić, Slavica
AU  - Ke, Song
AU  - Barata, Teresa
AU  - Solmajer, Tom
AU  - Antić-Stanković, Jelena
AU  - Juranić, Zorica
AU  - Savić, Vladimir
AU  - Zloh, Mire
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1727
AB  - A set of 16 previously synthesized aryl-aminopyridine and aryl-aminoquinoline derivatives have been evaluated for cytotoxic activity against three cancer cell lines (human cervical cancer-HeLa; human chronic myeloid leukemia-K562; human melanoma-Fem-x) and two types of normal peripheral blood mononuclear cells, with and without phytohemaglutinin (PBMC - PHA; PBMC + PHA). Twelve of the studied compounds showed moderate cytotoxicity, with selectivity against K562 but not the remaining two cancer cell lines. Four compounds were not active in cytotoxicity assays, presumably due to high predicted lipophilicity and low solubility. To rationalize the observed cytotoxic effects, structure-based virtual screening was carried out against a pool of potential targets constructed using the inverse docking program Tarfisdock and bibliographical references. The putative targets were identified on the basis of the best correlation between docking scores and in vitro cytotoxicity. It is proposed that the mechanism of action of the studied aminopyridines involves the disruption of signaling pathways and cancer cell cycle through the inhibition of cyclin-dependent kinases and several tyrosine kinases, namely Bcr-Abl kinase and KIT receptor kinase. The obtained results can guide further structural modifications of the studied compounds aimed at developing selective agents targeting proteins involved in cancer cell survival and proliferation.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & Medicinal Chemistry
T1  - Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity
VL  - 20
IS  - 17
SP  - 5220
EP  - 5228
DO  - 10.1016/j.bmc.2012.06.051
ER  - 

@article{
author = "Erić, Slavica and Ke, Song and Barata, Teresa and Solmajer, Tom and Antić-Stanković, Jelena and Juranić, Zorica and Savić, Vladimir and Zloh, Mire",
year = "2012",
abstract = "A set of 16 previously synthesized aryl-aminopyridine and aryl-aminoquinoline derivatives have been evaluated for cytotoxic activity against three cancer cell lines (human cervical cancer-HeLa; human chronic myeloid leukemia-K562; human melanoma-Fem-x) and two types of normal peripheral blood mononuclear cells, with and without phytohemaglutinin (PBMC - PHA; PBMC + PHA). Twelve of the studied compounds showed moderate cytotoxicity, with selectivity against K562 but not the remaining two cancer cell lines. Four compounds were not active in cytotoxicity assays, presumably due to high predicted lipophilicity and low solubility. To rationalize the observed cytotoxic effects, structure-based virtual screening was carried out against a pool of potential targets constructed using the inverse docking program Tarfisdock and bibliographical references. The putative targets were identified on the basis of the best correlation between docking scores and in vitro cytotoxicity. It is proposed that the mechanism of action of the studied aminopyridines involves the disruption of signaling pathways and cancer cell cycle through the inhibition of cyclin-dependent kinases and several tyrosine kinases, namely Bcr-Abl kinase and KIT receptor kinase. The obtained results can guide further structural modifications of the studied compounds aimed at developing selective agents targeting proteins involved in cancer cell survival and proliferation.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & Medicinal Chemistry",
title = "Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity",
volume = "20",
number = "17",
pages = "5220-5228",
doi = "10.1016/j.bmc.2012.06.051"
}

Erić, S., Ke, S., Barata, T., Solmajer, T., Antić-Stanković, J., Juranić, Z., Savić, V.,& Zloh, M.. (2012). Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity. in Bioorganic & Medicinal Chemistry
Pergamon-Elsevier Science Ltd, Oxford., 20(17), 5220-5228.
https://doi.org/10.1016/j.bmc.2012.06.051

Erić S, Ke S, Barata T, Solmajer T, Antić-Stanković J, Juranić Z, Savić V, Zloh M. Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity. in Bioorganic & Medicinal Chemistry. 2012;20(17):5220-5228.
doi:10.1016/j.bmc.2012.06.051 .

Erić, Slavica, Ke, Song, Barata, Teresa, Solmajer, Tom, Antić-Stanković, Jelena, Juranić, Zorica, Savić, Vladimir, Zloh, Mire, "Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity" in Bioorganic & Medicinal Chemistry, 20, no. 17 (2012):5220-5228,
https://doi.org/10.1016/j.bmc.2012.06.051 . .

TY  - JOUR
AU  - Erić, Slavica
AU  - Kalinić, Marko
AU  - Popović, Aleksandar
AU  - Zloh, Mire
AU  - Kuzmanovski, Igor
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1644
AB  - In this work, we present a novel approach for the development of models for prediction of aqueous solubility, based on the implementation of an algorithm for the automatic adjustment of descriptor's relative importance (AARI) in counter-propagation artificial neural networks (CPANN). Using this approach, the interpretability of the models based on artificial neural networks, which are traditionally considered as "black box" models, was significantly improved. For the development of the model, a data set consisting of 374 diverse drug-like molecules, divided into training (n = 280) and test (n = 94) sets using self-organizing maps, was used. Heuristic method was applied in preselecting a small number of the most significant descriptors to serve as inputs for CPANN training. The performances of the final model based on 7 descriptors for prediction of solubility were satisfactory for both training (RMSEPtrain = 0.668) and test set (RMSEPtest = 0.679). The model was found to be a highly interpretable in terms of solubility, as well as rationalizing structural features that could have an impact on the solubility of the compounds investigated. Therefore, the proposed approach can significantly enhance model usability by giving guidance for structural modifications of compounds with the aim of improving solubility in the early phase of drug discovery.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Prediction of aqueous solubility of drug-like molecules using a novel algorithm for automatic adjustment of relative importance of descriptors implemented in counter-propagation artificial neural networks
VL  - 437
IS  - 1-2
SP  - 232
EP  - 241
DO  - 10.1016/j.ijpharm.2012.08.022
ER  - 

@article{
author = "Erić, Slavica and Kalinić, Marko and Popović, Aleksandar and Zloh, Mire and Kuzmanovski, Igor",
year = "2012",
abstract = "In this work, we present a novel approach for the development of models for prediction of aqueous solubility, based on the implementation of an algorithm for the automatic adjustment of descriptor's relative importance (AARI) in counter-propagation artificial neural networks (CPANN). Using this approach, the interpretability of the models based on artificial neural networks, which are traditionally considered as "black box" models, was significantly improved. For the development of the model, a data set consisting of 374 diverse drug-like molecules, divided into training (n = 280) and test (n = 94) sets using self-organizing maps, was used. Heuristic method was applied in preselecting a small number of the most significant descriptors to serve as inputs for CPANN training. The performances of the final model based on 7 descriptors for prediction of solubility were satisfactory for both training (RMSEPtrain = 0.668) and test set (RMSEPtest = 0.679). The model was found to be a highly interpretable in terms of solubility, as well as rationalizing structural features that could have an impact on the solubility of the compounds investigated. Therefore, the proposed approach can significantly enhance model usability by giving guidance for structural modifications of compounds with the aim of improving solubility in the early phase of drug discovery.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Prediction of aqueous solubility of drug-like molecules using a novel algorithm for automatic adjustment of relative importance of descriptors implemented in counter-propagation artificial neural networks",
volume = "437",
number = "1-2",
pages = "232-241",
doi = "10.1016/j.ijpharm.2012.08.022"
}

Erić, S., Kalinić, M., Popović, A., Zloh, M.,& Kuzmanovski, I.. (2012). Prediction of aqueous solubility of drug-like molecules using a novel algorithm for automatic adjustment of relative importance of descriptors implemented in counter-propagation artificial neural networks. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 437(1-2), 232-241.
https://doi.org/10.1016/j.ijpharm.2012.08.022

Erić S, Kalinić M, Popović A, Zloh M, Kuzmanovski I. Prediction of aqueous solubility of drug-like molecules using a novel algorithm for automatic adjustment of relative importance of descriptors implemented in counter-propagation artificial neural networks. in International Journal of Pharmaceutics. 2012;437(1-2):232-241.
doi:10.1016/j.ijpharm.2012.08.022 .

Erić, Slavica, Kalinić, Marko, Popović, Aleksandar, Zloh, Mire, Kuzmanovski, Igor, "Prediction of aqueous solubility of drug-like molecules using a novel algorithm for automatic adjustment of relative importance of descriptors implemented in counter-propagation artificial neural networks" in International Journal of Pharmaceutics, 437, no. 1-2 (2012):232-241,
https://doi.org/10.1016/j.ijpharm.2012.08.022 . .

TY  - JOUR
AU  - Drakulić, Branko
AU  - Juranić, Ivan O.
AU  - Erić, Slavica
AU  - Zloh, Mire
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1029
AB  - The use of chemical penetration enhancers (CPE) is growing due to their ability to improve drug delivery through the skin. A possible mechanism of penetration enhancement could involve the complex formation between drug and components in the pharmaceutical formulation, thus altering the physicochemical properties of the active substance. Here, modelling studies indicate that hydrocarbon and oxygen-containing terpenes (penetration enhancers) could form complexes with drugs. Satisfactory correlations have been obtained between the predicted molecular properties of enhancers and their enhancement effects. Crown Copyright
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Role of complexes formation between drugs and penetration enhancers in transdermal delivery
VL  - 363
IS  - 1-2
SP  - 40
EP  - 49
DO  - 10.1016/j.ijpharm.2008.06.032
ER  - 

@article{
author = "Drakulić, Branko and Juranić, Ivan O. and Erić, Slavica and Zloh, Mire",
year = "2008",
abstract = "The use of chemical penetration enhancers (CPE) is growing due to their ability to improve drug delivery through the skin. A possible mechanism of penetration enhancement could involve the complex formation between drug and components in the pharmaceutical formulation, thus altering the physicochemical properties of the active substance. Here, modelling studies indicate that hydrocarbon and oxygen-containing terpenes (penetration enhancers) could form complexes with drugs. Satisfactory correlations have been obtained between the predicted molecular properties of enhancers and their enhancement effects. Crown Copyright",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Role of complexes formation between drugs and penetration enhancers in transdermal delivery",
volume = "363",
number = "1-2",
pages = "40-49",
doi = "10.1016/j.ijpharm.2008.06.032"
}

Drakulić, B., Juranić, I. O., Erić, S.,& Zloh, M.. (2008). Role of complexes formation between drugs and penetration enhancers in transdermal delivery. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 363(1-2), 40-49.
https://doi.org/10.1016/j.ijpharm.2008.06.032

Drakulić B, Juranić IO, Erić S, Zloh M. Role of complexes formation between drugs and penetration enhancers in transdermal delivery. in International Journal of Pharmaceutics. 2008;363(1-2):40-49.
doi:10.1016/j.ijpharm.2008.06.032 .

Drakulić, Branko, Juranić, Ivan O., Erić, Slavica, Zloh, Mire, "Role of complexes formation between drugs and penetration enhancers in transdermal delivery" in International Journal of Pharmaceutics, 363, no. 1-2 (2008):40-49,
https://doi.org/10.1016/j.ijpharm.2008.06.032 . .

TY  - JOUR
AU  - Verbić, Tatjana Ž.
AU  - Drakulić, Branko
AU  - Zloh, Mire
AU  - Pecelj, Jovana R.
AU  - Popović, Gordana
AU  - Juranić, Ivan O.
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/997
AB  - The protolytic equilibria of 13 4-aryl-2,4-dioxobutanoic acids (ADKs) were spectrophotometrically studied in aqueous solutions in the pH range 1-9 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl), with the exception of the 4-OH-derivative which was also potentiometrically studied in the pH range 7-10 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl). In solution, the compounds simultaneously exist in one diketo and two enolic forms; therefore, the determined acidity constants (pKa1 1.87-2.29, pKa2 6.63-8.13 and pKa3(4-OH-) 9.52) represent system macro constants. The 1H-NMR spectrum of the parent compound (4-phenyl- -2,4-dioxobutanoic acid) (25 °C, pD 5.0) proved the existence of all tautomeric forms. Using the extended Hammett relation, the determined pKa values were correlated with literature σ values. The predicted pKa values were in fair accordance with the experimentally observed ones. Molecular, monoanionic and dianionic forms of the parent compound were optimized by the semi-empirical molecular orbital PM6 method using the implicit water solvation model (COSMO). The obtained geometries were used to explain the quality of the LFER models.
AB  - Protolitičke ravnoteže 13 jedinjenja iz klase 4-aril-2,4-dioksobutanskih kiselina (ADK) spektrofotometrijski su proučavane u vodenim rastvorima u pH intervalu 1-9 pri temperaturi 25±1 °C i jonskoj jačini rastvora 0.1 mol l-1 (NaCl), sa izuzetkom 4-OH-derivata koji je proučavan i potenciometrijski u pH intervalu 7-10 pri istim uslovima. Kako ADK u vodenom rastvoru podležu keto-enolnoj tautomeriji i istovremeno postoje u diketo i dva enolna oblika, to određene kiselinske konstante (pKa1 1.87-2.29, pKa2 6.63-8.13 i pKa3(4-OH-) 9.52) predstavljaju makro konstante za dati sistem. 1H-NMR spektar osnovne supstance (4-fenil-2,4-dioksobutanska kiselina) (25 °C, pD 5.0) potvrđuje prisustvo svih tautomernih oblika. Upotrebom proširene Hametove korelacije, određene pKa vrednosti korelisane su sa literaturnim σ vrednostima. Predviđene pKa vrednosti dobro se slažu sa eksperimentalno dobijenim. Molekulski, monoanjonski i dianjonski oblici osnovne supstance su optimizovani semiempirijskom molekulsko-orbitalnom PM6 metodom sa implicitnim modelom solvatacije u vodi (COSMO). Dobijene geometrije su upotrebljene za objašnjenje kvaliteta LFER modela.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - An LFER study of the protolytic equilibria of 4-aryl-2,4-dioxobutanoic acids in aqueous solutions
T1  - Linearne korelacije slobodne energije (LFER) protolitičkih ravnoteža 4-aril-2,4-dioksobutanskih kiselina u vodenim rastvorima
VL  - 72
IS  - 12
SP  - 1201
EP  - 1216
DO  - 10.2298/JSC0712201V
ER  - 

@article{
author = "Verbić, Tatjana Ž. and Drakulić, Branko and Zloh, Mire and Pecelj, Jovana R. and Popović, Gordana and Juranić, Ivan O.",
year = "2007",
abstract = "The protolytic equilibria of 13 4-aryl-2,4-dioxobutanoic acids (ADKs) were spectrophotometrically studied in aqueous solutions in the pH range 1-9 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl), with the exception of the 4-OH-derivative which was also potentiometrically studied in the pH range 7-10 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl). In solution, the compounds simultaneously exist in one diketo and two enolic forms; therefore, the determined acidity constants (pKa1 1.87-2.29, pKa2 6.63-8.13 and pKa3(4-OH-) 9.52) represent system macro constants. The 1H-NMR spectrum of the parent compound (4-phenyl- -2,4-dioxobutanoic acid) (25 °C, pD 5.0) proved the existence of all tautomeric forms. Using the extended Hammett relation, the determined pKa values were correlated with literature σ values. The predicted pKa values were in fair accordance with the experimentally observed ones. Molecular, monoanionic and dianionic forms of the parent compound were optimized by the semi-empirical molecular orbital PM6 method using the implicit water solvation model (COSMO). The obtained geometries were used to explain the quality of the LFER models., Protolitičke ravnoteže 13 jedinjenja iz klase 4-aril-2,4-dioksobutanskih kiselina (ADK) spektrofotometrijski su proučavane u vodenim rastvorima u pH intervalu 1-9 pri temperaturi 25±1 °C i jonskoj jačini rastvora 0.1 mol l-1 (NaCl), sa izuzetkom 4-OH-derivata koji je proučavan i potenciometrijski u pH intervalu 7-10 pri istim uslovima. Kako ADK u vodenom rastvoru podležu keto-enolnoj tautomeriji i istovremeno postoje u diketo i dva enolna oblika, to određene kiselinske konstante (pKa1 1.87-2.29, pKa2 6.63-8.13 i pKa3(4-OH-) 9.52) predstavljaju makro konstante za dati sistem. 1H-NMR spektar osnovne supstance (4-fenil-2,4-dioksobutanska kiselina) (25 °C, pD 5.0) potvrđuje prisustvo svih tautomernih oblika. Upotrebom proširene Hametove korelacije, određene pKa vrednosti korelisane su sa literaturnim σ vrednostima. Predviđene pKa vrednosti dobro se slažu sa eksperimentalno dobijenim. Molekulski, monoanjonski i dianjonski oblici osnovne supstance su optimizovani semiempirijskom molekulsko-orbitalnom PM6 metodom sa implicitnim modelom solvatacije u vodi (COSMO). Dobijene geometrije su upotrebljene za objašnjenje kvaliteta LFER modela.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "An LFER study of the protolytic equilibria of 4-aryl-2,4-dioxobutanoic acids in aqueous solutions, Linearne korelacije slobodne energije (LFER) protolitičkih ravnoteža 4-aril-2,4-dioksobutanskih kiselina u vodenim rastvorima",
volume = "72",
number = "12",
pages = "1201-1216",
doi = "10.2298/JSC0712201V"
}

Verbić, T. Ž., Drakulić, B., Zloh, M., Pecelj, J. R., Popović, G.,& Juranić, I. O.. (2007). An LFER study of the protolytic equilibria of 4-aryl-2,4-dioxobutanoic acids in aqueous solutions. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 72(12), 1201-1216.
https://doi.org/10.2298/JSC0712201V

Verbić TŽ, Drakulić B, Zloh M, Pecelj JR, Popović G, Juranić IO. An LFER study of the protolytic equilibria of 4-aryl-2,4-dioxobutanoic acids in aqueous solutions. in Journal of the Serbian Chemical Society. 2007;72(12):1201-1216.
doi:10.2298/JSC0712201V .

Verbić, Tatjana Ž., Drakulić, Branko, Zloh, Mire, Pecelj, Jovana R., Popović, Gordana, Juranić, Ivan O., "An LFER study of the protolytic equilibria of 4-aryl-2,4-dioxobutanoic acids in aqueous solutions" in Journal of the Serbian Chemical Society, 72, no. 12 (2007):1201-1216,
https://doi.org/10.2298/JSC0712201V . .