TY  - CHAP
AU  - Vemić, Ana
AU  - Kalinić, Marko
AU  - Čolović, Jelena
AU  - Erić, Slavica
AU  - Malenović, Anđelija
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3235
PB  - CRC Press-Taylor and Francis Group
T2  - Advances in Chromatography, Vol 54
T1  - Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications
VL  - 54
SP  - 1
EP  - 41
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3235
ER  - 

@inbook{
author = "Vemić, Ana and Kalinić, Marko and Čolović, Jelena and Erić, Slavica and Malenović, Anđelija",
year = "2018",
publisher = "CRC Press-Taylor and Francis Group",
journal = "Advances in Chromatography, Vol 54",
booktitle = "Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications",
volume = "54",
pages = "1-41",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3235"
}

Vemić, A., Kalinić, M., Čolović, J., Erić, S.,& Malenović, A.. (2018). Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications. in Advances in Chromatography, Vol 54
CRC Press-Taylor and Francis Group., 54, 1-41.
https://hdl.handle.net/21.15107/rcub_farfar_3235

Vemić A, Kalinić M, Čolović J, Erić S, Malenović A. Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications. in Advances in Chromatography, Vol 54. 2018;54:1-41.
https://hdl.handle.net/21.15107/rcub_farfar_3235 .

Vemić, Ana, Kalinić, Marko, Čolović, Jelena, Erić, Slavica, Malenović, Anđelija, "Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications" in Advances in Chromatography, Vol 54, 54 (2018):1-41,
https://hdl.handle.net/21.15107/rcub_farfar_3235 .

TY  - JOUR
AU  - Colović, Jelena
AU  - Kalinić, Marko
AU  - Vemić, Ana
AU  - Erić, Slavica
AU  - Malenović, Anđelija
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2807
AB  - In this study, we present novel insights into the pH-dependent retention behavior of protonated basic solutes in chaotropic chromatography. To this end, two sets of experiments were performed to distinguish between mobile phase pH and ionic strength effects. In the first set, the ionic strength (I) was varied with the concentration of NaPF6 and additives that adjusted the mobile phase pH, while in the second set, I was kept constant by adding the appropriate amount of NaCl. In each set, the retention behavior of 13 analytes was qualitatively examined in 21 chromatographic systems, which were defined by the NaPF6 concentration in their aqueous phases (1-50 mM) and the pH of their mobile phases (2,3 or 4); the acetonitrile content was fixed at 40%. The addition of NaCl significantly reduced the differences among retention factors at studied pH values due to the effect of the Na+ ions on PF6- adsorption to the stationary phase and the magnitude of the consequential development of the surface potential. A quantitative description of the observed phenomenon was obtained by an extended thermodynamic approach. The contribution of ion-pair formation in the stationary phase to the retention of the solutes was confirmed across models at the studied pH values in the set with varying I In the systems with a constant I, the shielding effect of the Na+ ions on the surface charge lowered the attractive surface potential and diminished the aforementioned interactions and hence the effect of the mobile phase pH on analyte retention. Eventually, we developed a readily interpretable empirical retention model that simultaneously takes into account analyte molecular structures and the most relevant chromatographic factors. Its coefficients have clear physical meaning, and owing to its good predictive capabilities, the model could be successfully used to clarify the contributions of analyte molecular structures and chromatographic factors to the specific processes underlying separation in chaotropic chromatography.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography
VL  - 1511
SP  - 68
EP  - 76
DO  - 10.1016/j.chroma.2017.06.069
ER  - 

@article{
author = "Colović, Jelena and Kalinić, Marko and Vemić, Ana and Erić, Slavica and Malenović, Anđelija",
year = "2017",
abstract = "In this study, we present novel insights into the pH-dependent retention behavior of protonated basic solutes in chaotropic chromatography. To this end, two sets of experiments were performed to distinguish between mobile phase pH and ionic strength effects. In the first set, the ionic strength (I) was varied with the concentration of NaPF6 and additives that adjusted the mobile phase pH, while in the second set, I was kept constant by adding the appropriate amount of NaCl. In each set, the retention behavior of 13 analytes was qualitatively examined in 21 chromatographic systems, which were defined by the NaPF6 concentration in their aqueous phases (1-50 mM) and the pH of their mobile phases (2,3 or 4); the acetonitrile content was fixed at 40%. The addition of NaCl significantly reduced the differences among retention factors at studied pH values due to the effect of the Na+ ions on PF6- adsorption to the stationary phase and the magnitude of the consequential development of the surface potential. A quantitative description of the observed phenomenon was obtained by an extended thermodynamic approach. The contribution of ion-pair formation in the stationary phase to the retention of the solutes was confirmed across models at the studied pH values in the set with varying I In the systems with a constant I, the shielding effect of the Na+ ions on the surface charge lowered the attractive surface potential and diminished the aforementioned interactions and hence the effect of the mobile phase pH on analyte retention. Eventually, we developed a readily interpretable empirical retention model that simultaneously takes into account analyte molecular structures and the most relevant chromatographic factors. Its coefficients have clear physical meaning, and owing to its good predictive capabilities, the model could be successfully used to clarify the contributions of analyte molecular structures and chromatographic factors to the specific processes underlying separation in chaotropic chromatography.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography",
volume = "1511",
pages = "68-76",
doi = "10.1016/j.chroma.2017.06.069"
}

Colović, J., Kalinić, M., Vemić, A., Erić, S.,& Malenović, A.. (2017). Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1511, 68-76.
https://doi.org/10.1016/j.chroma.2017.06.069

Colović J, Kalinić M, Vemić A, Erić S, Malenović A. Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography. in Journal of Chromatography A. 2017;1511:68-76.
doi:10.1016/j.chroma.2017.06.069 .

Colović, Jelena, Kalinić, Marko, Vemić, Ana, Erić, Slavica, Malenović, Anđelija, "Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography" in Journal of Chromatography A, 1511 (2017):68-76,
https://doi.org/10.1016/j.chroma.2017.06.069 . .

TY  - JOUR
AU  - Simić, Milena
AU  - Damjanović, Ana B.
AU  - Kalinić, Marko
AU  - Tasić, Gordana
AU  - Erić, Slavica
AU  - Antić-Stanković, Jelena
AU  - Savić, Vladimir
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2606
AB  - A novel and efficient synthetic route was developed for the preparation of protoberberine derivatives. A methodology, designed primarily to control the substitution patterns on the terminal rings, was used to access a small array of these compounds. An initial biological profiling suggested an anticancer potential of the synthesised derivatives, while structure-based target fishing identified their potential targets and established a rational basis for further structural modifications. Although the activities need further improvement, the study demonstrated that the described approach may be useful in the discovery of novel lead compounds.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis, cytotoxicity and computational study of novel protoberberine derivatives
VL  - 81
IS  - 2
SP  - 103
EP  - 123
DO  - 10.2298/JSC150525090S
ER  - 

@article{
author = "Simić, Milena and Damjanović, Ana B. and Kalinić, Marko and Tasić, Gordana and Erić, Slavica and Antić-Stanković, Jelena and Savić, Vladimir",
year = "2016",
abstract = "A novel and efficient synthetic route was developed for the preparation of protoberberine derivatives. A methodology, designed primarily to control the substitution patterns on the terminal rings, was used to access a small array of these compounds. An initial biological profiling suggested an anticancer potential of the synthesised derivatives, while structure-based target fishing identified their potential targets and established a rational basis for further structural modifications. Although the activities need further improvement, the study demonstrated that the described approach may be useful in the discovery of novel lead compounds.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis, cytotoxicity and computational study of novel protoberberine derivatives",
volume = "81",
number = "2",
pages = "103-123",
doi = "10.2298/JSC150525090S"
}

Simić, M., Damjanović, A. B., Kalinić, M., Tasić, G., Erić, S., Antić-Stanković, J.,& Savić, V.. (2016). Synthesis, cytotoxicity and computational study of novel protoberberine derivatives. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 81(2), 103-123.
https://doi.org/10.2298/JSC150525090S

Simić M, Damjanović AB, Kalinić M, Tasić G, Erić S, Antić-Stanković J, Savić V. Synthesis, cytotoxicity and computational study of novel protoberberine derivatives. in Journal of the Serbian Chemical Society. 2016;81(2):103-123.
doi:10.2298/JSC150525090S .

Simić, Milena, Damjanović, Ana B., Kalinić, Marko, Tasić, Gordana, Erić, Slavica, Antić-Stanković, Jelena, Savić, Vladimir, "Synthesis, cytotoxicity and computational study of novel protoberberine derivatives" in Journal of the Serbian Chemical Society, 81, no. 2 (2016):103-123,
https://doi.org/10.2298/JSC150525090S . .

TY  - JOUR
AU  - Tumpa, Anja
AU  - Kalinić, Marko
AU  - Jovanović, Predrag
AU  - Erić, Slavica
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
AU  - Medenica, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2650
AB  - In this article, retention modeling of eight aminopyridines (synthesized and characterized at the Faculty of Pharmacy) in reversed-phase high performance liquid chromatography (RP-HPLC) was performed. No data related to their retention in the RP-HPLC system were found. Knowing that, it was recognized as very important to describe their retention behavior. The influences of pH of the mobile phase and the organic modifier content on the retention factors were investigated. Two theoretical models for the dependence of retention factor of organic modifier content were tested. Then, the most reliable and accurate prediction of log k was created, testing multiple linear regression model-quantitative structure-retention relationships (MLR-QSRR) and support vector regression machine-quantitative structure-retention relationships (SVM-QSRR). Initially, 400 descriptors were calculated, but four of them (POM, log D, M-SZX/RZX and m-RPCG) were included in the models. SVM-QSRR performed significantly better than the MLR model. Apart from aminopyridines, four structurally similar substances (indapamide, gliclazide, sulfamethoxazole and furosemide) were followed in the same chromatographic system. They were used as external validation set for the QSRR model (it performed well within its applicability domain, which was defined using a bounding box approach). After having described retention of eight aminopyridines with both theoretical and QSRR models, further investigations in this field can be conducted.
PB  - Oxford Univ Press Inc, Cary
T2  - Journal of Chromatographic Science
T1  - Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines
VL  - 54
IS  - 3
SP  - 436
EP  - 444
DO  - 10.1093/chromsci/bmv165
ER  - 

@article{
author = "Tumpa, Anja and Kalinić, Marko and Jovanović, Predrag and Erić, Slavica and Rakić, Tijana and Jančić-Stojanović, Biljana and Medenica, Mirjana",
year = "2016",
abstract = "In this article, retention modeling of eight aminopyridines (synthesized and characterized at the Faculty of Pharmacy) in reversed-phase high performance liquid chromatography (RP-HPLC) was performed. No data related to their retention in the RP-HPLC system were found. Knowing that, it was recognized as very important to describe their retention behavior. The influences of pH of the mobile phase and the organic modifier content on the retention factors were investigated. Two theoretical models for the dependence of retention factor of organic modifier content were tested. Then, the most reliable and accurate prediction of log k was created, testing multiple linear regression model-quantitative structure-retention relationships (MLR-QSRR) and support vector regression machine-quantitative structure-retention relationships (SVM-QSRR). Initially, 400 descriptors were calculated, but four of them (POM, log D, M-SZX/RZX and m-RPCG) were included in the models. SVM-QSRR performed significantly better than the MLR model. Apart from aminopyridines, four structurally similar substances (indapamide, gliclazide, sulfamethoxazole and furosemide) were followed in the same chromatographic system. They were used as external validation set for the QSRR model (it performed well within its applicability domain, which was defined using a bounding box approach). After having described retention of eight aminopyridines with both theoretical and QSRR models, further investigations in this field can be conducted.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Journal of Chromatographic Science",
title = "Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines",
volume = "54",
number = "3",
pages = "436-444",
doi = "10.1093/chromsci/bmv165"
}

Tumpa, A., Kalinić, M., Jovanović, P., Erić, S., Rakić, T., Jančić-Stojanović, B.,& Medenica, M.. (2016). Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines. in Journal of Chromatographic Science
Oxford Univ Press Inc, Cary., 54(3), 436-444.
https://doi.org/10.1093/chromsci/bmv165

Tumpa A, Kalinić M, Jovanović P, Erić S, Rakić T, Jančić-Stojanović B, Medenica M. Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines. in Journal of Chromatographic Science. 2016;54(3):436-444.
doi:10.1093/chromsci/bmv165 .

Tumpa, Anja, Kalinić, Marko, Jovanović, Predrag, Erić, Slavica, Rakić, Tijana, Jančić-Stojanović, Biljana, Medenica, Mirjana, "Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines" in Journal of Chromatographic Science, 54, no. 3 (2016):436-444,
https://doi.org/10.1093/chromsci/bmv165 . .

TY  - JOUR
AU  - Erić, Slavica
AU  - Kalinić, Marko
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2515
AB  - P-glycoprotein (Pgp) is a transmembrane transporter which can, by transporting structurally diverse compounds, influence the absorption, distribution and efficacy of a number of drugs. Pgp overexpression in cells is a major contributing factor to the development of drug resistance. For these reasons, potential for compound efflux by Pgp should be assessed early on in the drug discovery process, preferably even prior to compound synthesis. To meet this demand, numerous computational models have been developed during the past decade, capable of predicting Pgp-mediated transport based solely on chemical structures. This paper summarizes the various approaches that have been used for model development, discusses their advantages and disadvantages and focuses on key factors that influence model reliability. The promiscuous nature of the transport can be seen as a major challenge for most computational chemistry methods. Nevertheless, the attained level of accuracy of literature models suggests that they can be useful in the drug discovery setting. Greater availability of experimental data and integration of predictions made by different modeling methods has the potential to further improve the reliability of computational predictions.
AB  - P-glikoprotein (Pgp) je transmembranski transporter koji, transportujući strukturno raznovrsne lekove iz unutrašnjosti ćelije u ekstracelularnu sredinu, može uticati na resorpciju, distribuciju i efikasnost većeg broja lekova. Prekomerna ekspresija Pgp-a u ćelijama predstavlja jedan od mehanizama razvoja rezistencije na lekove. Iz ovih razloga, potrebno je u ranoj fazi otkrića leka predvideti da li je potencijalni lek supstrat za Pgp, idealno i pre same sinteze. U tu svrhu, tokom poslednje decenije razvijen je veliki broj računarskih modela koji omogućavaju predviđanje transporta posredstvom Pgp-a samo na osnovu hemijske strukture. U ovom radu prikazan je pregled različitih pristupa koji su korišćeni u razvoju modela, razmotrene su njihove prednosti i nedostaci, kao i faktori koji u najvećoj meri utiču na pouzdanost predviđanja. Polispecifičnost ovog transportera predstavlja značajan izazov za većinu metoda računarske hemije. Ipak, dostignut nivo tačnosti modela koji su prikazani u litearaturi ukazuje na činjenicu da oni mogu doprineti racionalizaciji procesa dizajniranja novih lekova. Šira dostupnost eksperimentalnih podataka, kao i kombinovanje različitih pristupa modelovanju transporta, mogu dodatno unaprediti postojeće modele.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Computational models for predicting drug transport mediated by P-glycoprotein
T1  - Računarski modeli za predviđanje transporta lekova posredovanog P-glikoproteinom
VL  - 65
IS  - 2
SP  - 89
EP  - 114
DO  - 10.5937/arhfarm1502089E
ER  - 

@article{
author = "Erić, Slavica and Kalinić, Marko",
year = "2015",
abstract = "P-glycoprotein (Pgp) is a transmembrane transporter which can, by transporting structurally diverse compounds, influence the absorption, distribution and efficacy of a number of drugs. Pgp overexpression in cells is a major contributing factor to the development of drug resistance. For these reasons, potential for compound efflux by Pgp should be assessed early on in the drug discovery process, preferably even prior to compound synthesis. To meet this demand, numerous computational models have been developed during the past decade, capable of predicting Pgp-mediated transport based solely on chemical structures. This paper summarizes the various approaches that have been used for model development, discusses their advantages and disadvantages and focuses on key factors that influence model reliability. The promiscuous nature of the transport can be seen as a major challenge for most computational chemistry methods. Nevertheless, the attained level of accuracy of literature models suggests that they can be useful in the drug discovery setting. Greater availability of experimental data and integration of predictions made by different modeling methods has the potential to further improve the reliability of computational predictions., P-glikoprotein (Pgp) je transmembranski transporter koji, transportujući strukturno raznovrsne lekove iz unutrašnjosti ćelije u ekstracelularnu sredinu, može uticati na resorpciju, distribuciju i efikasnost većeg broja lekova. Prekomerna ekspresija Pgp-a u ćelijama predstavlja jedan od mehanizama razvoja rezistencije na lekove. Iz ovih razloga, potrebno je u ranoj fazi otkrića leka predvideti da li je potencijalni lek supstrat za Pgp, idealno i pre same sinteze. U tu svrhu, tokom poslednje decenije razvijen je veliki broj računarskih modela koji omogućavaju predviđanje transporta posredstvom Pgp-a samo na osnovu hemijske strukture. U ovom radu prikazan je pregled različitih pristupa koji su korišćeni u razvoju modela, razmotrene su njihove prednosti i nedostaci, kao i faktori koji u najvećoj meri utiču na pouzdanost predviđanja. Polispecifičnost ovog transportera predstavlja značajan izazov za većinu metoda računarske hemije. Ipak, dostignut nivo tačnosti modela koji su prikazani u litearaturi ukazuje na činjenicu da oni mogu doprineti racionalizaciji procesa dizajniranja novih lekova. Šira dostupnost eksperimentalnih podataka, kao i kombinovanje različitih pristupa modelovanju transporta, mogu dodatno unaprediti postojeće modele.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Computational models for predicting drug transport mediated by P-glycoprotein, Računarski modeli za predviđanje transporta lekova posredovanog P-glikoproteinom",
volume = "65",
number = "2",
pages = "89-114",
doi = "10.5937/arhfarm1502089E"
}

Erić, S.,& Kalinić, M.. (2015). Computational models for predicting drug transport mediated by P-glycoprotein. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 65(2), 89-114.
https://doi.org/10.5937/arhfarm1502089E

Erić S, Kalinić M. Computational models for predicting drug transport mediated by P-glycoprotein. in Arhiv za farmaciju. 2015;65(2):89-114.
doi:10.5937/arhfarm1502089E .

Erić, Slavica, Kalinić, Marko, "Computational models for predicting drug transport mediated by P-glycoprotein" in Arhiv za farmaciju, 65, no. 2 (2015):89-114,
https://doi.org/10.5937/arhfarm1502089E . .

TY  - JOUR
AU  - Vemić, Ana
AU  - Kalinić, Marko
AU  - Erić, Slavica
AU  - Malenović, Anđelija
AU  - Medenica, Mirjana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2383
AB  - The aim of this study was to examine the interaction of the chaotropic salts of different position in Hofmeister series (CF3COONa, NaClO4, NaPF6) added to the mobile phase with the stationary phases of different hydrophobicity (C8 and C18 XTerra (R) columns), as well as their common influence on the retention behavior of pramipexole and its structurally related impurities. The extended thermodynamic approach enabled the understanding of the underlying separation mechanism. Comparing six different column-salt systems it was observed that general system hydrophobicity presented by salt chaotropicity and column hydrophobicity favors stationary phase ion-pairing over the ion-pair formation in the eluent. Further, an attempt was made to describe the influence of analytes' nature on their retention behavior in such chromatographic systems. An analysis is performed in order to select and elucidate the molecular descriptors (electrostatical, quantum-chemical, geometrical, topological, and constitutional) that best explain the experimental evidence and findings obtained by the thermodynamic approach. The results of this analysis suggest that analytes' charge distribution and its complementarity to the structure of the electric double layer formed on the surface of the stationary phase upon the addition of chaotropic additives can be useful for understanding the differences in retention of structurally related analytes. These findings provide a novel understanding of the interactions between all the components of the chromatographic system containing chaotropic additive and a good basis for further investigations suggesting the development of generally applicable predictors in structure-retention relationship studies in related chromatographic systems.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - The influence of salt chaotropicity, column hydrophobicity and analytes' molecular properties on the retention of pramipexole and its impurities
VL  - 1386
SP  - 39
EP  - 46
DO  - 10.1016/j.chroma.2015.01.078
ER  - 

@article{
author = "Vemić, Ana and Kalinić, Marko and Erić, Slavica and Malenović, Anđelija and Medenica, Mirjana",
year = "2015",
abstract = "The aim of this study was to examine the interaction of the chaotropic salts of different position in Hofmeister series (CF3COONa, NaClO4, NaPF6) added to the mobile phase with the stationary phases of different hydrophobicity (C8 and C18 XTerra (R) columns), as well as their common influence on the retention behavior of pramipexole and its structurally related impurities. The extended thermodynamic approach enabled the understanding of the underlying separation mechanism. Comparing six different column-salt systems it was observed that general system hydrophobicity presented by salt chaotropicity and column hydrophobicity favors stationary phase ion-pairing over the ion-pair formation in the eluent. Further, an attempt was made to describe the influence of analytes' nature on their retention behavior in such chromatographic systems. An analysis is performed in order to select and elucidate the molecular descriptors (electrostatical, quantum-chemical, geometrical, topological, and constitutional) that best explain the experimental evidence and findings obtained by the thermodynamic approach. The results of this analysis suggest that analytes' charge distribution and its complementarity to the structure of the electric double layer formed on the surface of the stationary phase upon the addition of chaotropic additives can be useful for understanding the differences in retention of structurally related analytes. These findings provide a novel understanding of the interactions between all the components of the chromatographic system containing chaotropic additive and a good basis for further investigations suggesting the development of generally applicable predictors in structure-retention relationship studies in related chromatographic systems.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "The influence of salt chaotropicity, column hydrophobicity and analytes' molecular properties on the retention of pramipexole and its impurities",
volume = "1386",
pages = "39-46",
doi = "10.1016/j.chroma.2015.01.078"
}

Vemić, A., Kalinić, M., Erić, S., Malenović, A.,& Medenica, M.. (2015). The influence of salt chaotropicity, column hydrophobicity and analytes' molecular properties on the retention of pramipexole and its impurities. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1386, 39-46.
https://doi.org/10.1016/j.chroma.2015.01.078

Vemić A, Kalinić M, Erić S, Malenović A, Medenica M. The influence of salt chaotropicity, column hydrophobicity and analytes' molecular properties on the retention of pramipexole and its impurities. in Journal of Chromatography A. 2015;1386:39-46.
doi:10.1016/j.chroma.2015.01.078 .

Vemić, Ana, Kalinić, Marko, Erić, Slavica, Malenović, Anđelija, Medenica, Mirjana, "The influence of salt chaotropicity, column hydrophobicity and analytes' molecular properties on the retention of pramipexole and its impurities" in Journal of Chromatography A, 1386 (2015):39-46,
https://doi.org/10.1016/j.chroma.2015.01.078 . .

TY  - JOUR
AU  - Colović, Jelena
AU  - Kalinić, Marko
AU  - Vemić, Ana
AU  - Erić, Slavica
AU  - Malenović, Anđelija
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2365
AB  - The aim of this study was to systematically investigate the phenomena affecting the retention behavior of structurally diverse basic drugs in ion-interaction chromatographic systems with chaotropic additives. To this end, the influence of three factors was studied: pH value of the aqueous phase, concentration of sodium hexafluorophosphate, and content of acetonitrile in the mobile phase. Mobile phase pH was found to affect the thermodynamic equilibria in the studied system beyond its effects on the analytes' ionization state. Specifically, increasing pH from 2 to 4 led to longer retention times, even with analytes which remain completely protonated. An explanation for this phenomenon was sought by studying the adsorption behavior of acetonitrile and chaotropic additive onto stationary phase. It was shown that the magnitude of the developed surface potential, which significantly affects retention - increases with pH, and that this can be attributed to the larger surface excess of acetonitrile. To study how analytes' structural properties influence their retention, quantitative structure-retention modeling was performed next. A support vector machine regression model was developed, relating mobile phase constituents and structural descriptors with retention data. While the ETA_EtaP_B_RC and XlogP can be considered as molecular descriptors which describe factors affecting retention in any RP-HPLC system, TDB9p and RDF45p are molecular descriptors which account for spatial arrangement of polarizable atoms and they can clearly relate to analytes' behavior on the stationary phase surface, where the electrostatic potential develops. Complementarity of analytes' structure with that of the electric double layer can be seen as a key factor influencing their retention behavior. Structural diversity of analytes and good predictive capabilities over a range of experimental conditions make the established model a useful tool in predicting retention behavior in the studied chromatographic system.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties
VL  - 1425
SP  - 150
EP  - 157
DO  - 10.1016/j.chroma.2015.11.027
ER  - 

@article{
author = "Colović, Jelena and Kalinić, Marko and Vemić, Ana and Erić, Slavica and Malenović, Anđelija",
year = "2015",
abstract = "The aim of this study was to systematically investigate the phenomena affecting the retention behavior of structurally diverse basic drugs in ion-interaction chromatographic systems with chaotropic additives. To this end, the influence of three factors was studied: pH value of the aqueous phase, concentration of sodium hexafluorophosphate, and content of acetonitrile in the mobile phase. Mobile phase pH was found to affect the thermodynamic equilibria in the studied system beyond its effects on the analytes' ionization state. Specifically, increasing pH from 2 to 4 led to longer retention times, even with analytes which remain completely protonated. An explanation for this phenomenon was sought by studying the adsorption behavior of acetonitrile and chaotropic additive onto stationary phase. It was shown that the magnitude of the developed surface potential, which significantly affects retention - increases with pH, and that this can be attributed to the larger surface excess of acetonitrile. To study how analytes' structural properties influence their retention, quantitative structure-retention modeling was performed next. A support vector machine regression model was developed, relating mobile phase constituents and structural descriptors with retention data. While the ETA_EtaP_B_RC and XlogP can be considered as molecular descriptors which describe factors affecting retention in any RP-HPLC system, TDB9p and RDF45p are molecular descriptors which account for spatial arrangement of polarizable atoms and they can clearly relate to analytes' behavior on the stationary phase surface, where the electrostatic potential develops. Complementarity of analytes' structure with that of the electric double layer can be seen as a key factor influencing their retention behavior. Structural diversity of analytes and good predictive capabilities over a range of experimental conditions make the established model a useful tool in predicting retention behavior in the studied chromatographic system.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties",
volume = "1425",
pages = "150-157",
doi = "10.1016/j.chroma.2015.11.027"
}

Colović, J., Kalinić, M., Vemić, A., Erić, S.,& Malenović, A.. (2015). Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1425, 150-157.
https://doi.org/10.1016/j.chroma.2015.11.027

Colović J, Kalinić M, Vemić A, Erić S, Malenović A. Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties. in Journal of Chromatography A. 2015;1425:150-157.
doi:10.1016/j.chroma.2015.11.027 .

Colović, Jelena, Kalinić, Marko, Vemić, Ana, Erić, Slavica, Malenović, Anđelija, "Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties" in Journal of Chromatography A, 1425 (2015):150-157,
https://doi.org/10.1016/j.chroma.2015.11.027 . .

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  - Basić, J.
AU  - Kalinić, Marko
AU  - Ivković, Branka
AU  - Erić, Slavica
AU  - Milenković, Marina
AU  - Vladimirov, S.
AU  - Vujić, Zorica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2114
AB  - Twelve 2'-hydroxy chalcones were synthesized and their in vitro antibacterial activity was tested using eight standard strains of bacteria: S. aureus (ATCC 25923), S. epidermidis (ATCC 12228), B. subtilis (ATCC 6633), M. luteus (ATCC 10240), M. flavus (ATCC 9341), E. faecalis (ATCC 29212), K. pneumoniae (NCIMB 9111) and P. aeruginosa (ATCC 27853). All 2'-hydroxy chalcones have shown moderate to good antimicrobial activity, determined by microdilution method. QSAR analysis was performed for all the cases, R-2 = 0.918 - 0.997. The results of our QSAR analysis indicate that an alternative and complementary mechanism of action is a major determinant of 2'-hydroxy chalcone antibacterial efficiency. These chalcone derivatives posses the ability to act as bidendate chelating agents whereby the ketone moiety forms a coordinate bond and the 2'-hydroxy group forms a covalent bond with a corresponding metal ion. Chelate formation can disrupt the function of bacterial metalloproteins wich may affect the further growth of bacterial cells.
PB  - Inst Materials Physics, Bucharest
T2  - Digest Journal of Nanomaterials and Biostructures
T1  - Synthesis, QSAR analysis and mechanism of antybacterial activity of simple 2 '-hydroxy chalcones
VL  - 9
IS  - 4
SP  - 1537
EP  - 1546
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2114
ER  - 

@article{
author = "Basić, J. and Kalinić, Marko and Ivković, Branka and Erić, Slavica and Milenković, Marina and Vladimirov, S. and Vujić, Zorica",
year = "2014",
abstract = "Twelve 2'-hydroxy chalcones were synthesized and their in vitro antibacterial activity was tested using eight standard strains of bacteria: S. aureus (ATCC 25923), S. epidermidis (ATCC 12228), B. subtilis (ATCC 6633), M. luteus (ATCC 10240), M. flavus (ATCC 9341), E. faecalis (ATCC 29212), K. pneumoniae (NCIMB 9111) and P. aeruginosa (ATCC 27853). All 2'-hydroxy chalcones have shown moderate to good antimicrobial activity, determined by microdilution method. QSAR analysis was performed for all the cases, R-2 = 0.918 - 0.997. The results of our QSAR analysis indicate that an alternative and complementary mechanism of action is a major determinant of 2'-hydroxy chalcone antibacterial efficiency. These chalcone derivatives posses the ability to act as bidendate chelating agents whereby the ketone moiety forms a coordinate bond and the 2'-hydroxy group forms a covalent bond with a corresponding metal ion. Chelate formation can disrupt the function of bacterial metalloproteins wich may affect the further growth of bacterial cells.",
publisher = "Inst Materials Physics, Bucharest",
journal = "Digest Journal of Nanomaterials and Biostructures",
title = "Synthesis, QSAR analysis and mechanism of antybacterial activity of simple 2 '-hydroxy chalcones",
volume = "9",
number = "4",
pages = "1537-1546",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2114"
}

Basić, J., Kalinić, M., Ivković, B., Erić, S., Milenković, M., Vladimirov, S.,& Vujić, Z.. (2014). Synthesis, QSAR analysis and mechanism of antybacterial activity of simple 2 '-hydroxy chalcones. in Digest Journal of Nanomaterials and Biostructures
Inst Materials Physics, Bucharest., 9(4), 1537-1546.
https://hdl.handle.net/21.15107/rcub_farfar_2114

Basić J, Kalinić M, Ivković B, Erić S, Milenković M, Vladimirov S, Vujić Z. Synthesis, QSAR analysis and mechanism of antybacterial activity of simple 2 '-hydroxy chalcones. in Digest Journal of Nanomaterials and Biostructures. 2014;9(4):1537-1546.
https://hdl.handle.net/21.15107/rcub_farfar_2114 .

Basić, J., Kalinić, Marko, Ivković, Branka, Erić, Slavica, Milenković, Marina, Vladimirov, S., Vujić, Zorica, "Synthesis, QSAR analysis and mechanism of antybacterial activity of simple 2 '-hydroxy chalcones" in Digest Journal of Nanomaterials and Biostructures, 9, no. 4 (2014):1537-1546,
https://hdl.handle.net/21.15107/rcub_farfar_2114 .

TY  - JOUR
AU  - Erić, Slavica
AU  - Kalinić, Marko
AU  - Savić, Vladimir
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1814
AB  - The action and fate of drugs in the organism are determined by their interactions with endogenous macromolecules which are predominantly chiral in character. Consideration of the stereochemical aspects of drug action and pharmacokinetics has been intensified since the 1980s and has led to extensive documentation of significant differences existing between stereoisomeric forms of a single drug. Enantiomers can posses different efficacies, exhibit different pharmacological and toxicological effects, and consequently be characterized by different safety profiles. The growing wealth of evidence on the importance of stereochemistry, regulatory incentives, development of asymmetric synthesis methods and analytics - all contributed to fundamental changes in the way new chiral drugs are developed, tested, registered and market-managed. Today, enantiomers need to be treated as separate chemical entities and investigated correspondingly. Development of single enantiomer drugs can facilitate the reduction of total dose of xenobiotic administered to patients; improve the accuracy of doseresponse estimation; simplify pharmacokinetic studies and therapeutic monitoring. The stereochemical characteristics of biologically active compounds should, therefore, be considered from the earliest stages of drug development. Based on the established impact of stereochemistry, a single enantiomer formulation should be favored, whenever justified.
AB  - Dejstvo i sudbina leka u organizmu zavise od hiralnosti samih lekova kao i endogenih makromolekula sa kojima stupaju u interakciju. Razmatranje stereohemijskih aspekata dejstva i farmakokinetike lekova intenzivirano je početkom 80-tih godina prošlog veka i doprinelo je opsežnom dokumentovanju značajnih razlika između stereoizomernih oblika jednog leka. Enantiomeri tako mogu posedovati različitu efikasnost, mogu ispoljavati drugačije farmakološke i toksikološke efekte i sledstveno mogu imati različite bezbednosne profile. Sve veći broj dokaza o važnosti stereohemije, podsticaji regulatornih agencija, razvoj metoda asimetrične sinteze i analitike - doveli su do suštinskih promena u načinu na koji se novi hiralni lekovi razvijaju, ispituju, registruju i tržišno plasiraju. Enantiomere je danas neophodno tretirati kao zasebne entitete i zasebno ih ispitivati. Razvoj enantiomerno čistih formulacija lekova može omogućiti smanjenje ukupne količine ksenobiotika kojoj se pacijent izlaže, omogućiti precizniju procenu odnosa doze i efekta, pojednostaviti farmakokinetička ispitivanja i terapijski monitoring. Stoga je stereohemijske osobine biološki aktivnih jedinjenja neophodno razmatrati od najranijih faza procesa stvaranja novog leka da bi se blagovremeno napravio racionalan izbor jednog enantiomera za terapijsku primenu, kad god je to opravdano.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Stereochemical aspects of drug action and pharmacokinetics
T1  - Stereohemijski aspekti dejstva i farmakokinetike lekova
VL  - 62
IS  - 5
SP  - 499
EP  - 521
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1814
ER  - 

@article{
author = "Erić, Slavica and Kalinić, Marko and Savić, Vladimir",
year = "2012",
abstract = "The action and fate of drugs in the organism are determined by their interactions with endogenous macromolecules which are predominantly chiral in character. Consideration of the stereochemical aspects of drug action and pharmacokinetics has been intensified since the 1980s and has led to extensive documentation of significant differences existing between stereoisomeric forms of a single drug. Enantiomers can posses different efficacies, exhibit different pharmacological and toxicological effects, and consequently be characterized by different safety profiles. The growing wealth of evidence on the importance of stereochemistry, regulatory incentives, development of asymmetric synthesis methods and analytics - all contributed to fundamental changes in the way new chiral drugs are developed, tested, registered and market-managed. Today, enantiomers need to be treated as separate chemical entities and investigated correspondingly. Development of single enantiomer drugs can facilitate the reduction of total dose of xenobiotic administered to patients; improve the accuracy of doseresponse estimation; simplify pharmacokinetic studies and therapeutic monitoring. The stereochemical characteristics of biologically active compounds should, therefore, be considered from the earliest stages of drug development. Based on the established impact of stereochemistry, a single enantiomer formulation should be favored, whenever justified., Dejstvo i sudbina leka u organizmu zavise od hiralnosti samih lekova kao i endogenih makromolekula sa kojima stupaju u interakciju. Razmatranje stereohemijskih aspekata dejstva i farmakokinetike lekova intenzivirano je početkom 80-tih godina prošlog veka i doprinelo je opsežnom dokumentovanju značajnih razlika između stereoizomernih oblika jednog leka. Enantiomeri tako mogu posedovati različitu efikasnost, mogu ispoljavati drugačije farmakološke i toksikološke efekte i sledstveno mogu imati različite bezbednosne profile. Sve veći broj dokaza o važnosti stereohemije, podsticaji regulatornih agencija, razvoj metoda asimetrične sinteze i analitike - doveli su do suštinskih promena u načinu na koji se novi hiralni lekovi razvijaju, ispituju, registruju i tržišno plasiraju. Enantiomere je danas neophodno tretirati kao zasebne entitete i zasebno ih ispitivati. Razvoj enantiomerno čistih formulacija lekova može omogućiti smanjenje ukupne količine ksenobiotika kojoj se pacijent izlaže, omogućiti precizniju procenu odnosa doze i efekta, pojednostaviti farmakokinetička ispitivanja i terapijski monitoring. Stoga je stereohemijske osobine biološki aktivnih jedinjenja neophodno razmatrati od najranijih faza procesa stvaranja novog leka da bi se blagovremeno napravio racionalan izbor jednog enantiomera za terapijsku primenu, kad god je to opravdano.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Stereochemical aspects of drug action and pharmacokinetics, Stereohemijski aspekti dejstva i farmakokinetike lekova",
volume = "62",
number = "5",
pages = "499-521",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1814"
}

Erić, S., Kalinić, M.,& Savić, V.. (2012). Stereochemical aspects of drug action and pharmacokinetics. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 62(5), 499-521.
https://hdl.handle.net/21.15107/rcub_farfar_1814

Erić S, Kalinić M, Savić V. Stereochemical aspects of drug action and pharmacokinetics. in Arhiv za farmaciju. 2012;62(5):499-521.
https://hdl.handle.net/21.15107/rcub_farfar_1814 .

Erić, Slavica, Kalinić, Marko, Savić, Vladimir, "Stereochemical aspects of drug action and pharmacokinetics" in Arhiv za farmaciju, 62, no. 5 (2012):499-521,
https://hdl.handle.net/21.15107/rcub_farfar_1814 .

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  - Erić, Slavica
AU  - Kalinić, Marko
AU  - Popović, Aleksandar
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1446
AB  - Aqueous solubility of a drug is a factor which can significantly influence its oral bioavailability, and can also affect the drug distribution in the body. Consideration of aqueous solubility in early stages of drug discovery and development is vital in reducing the incidence of late-stage drug development failures. The application of computational models for solubility prediction could provide the screening of combinatorial libraries, helping single-out potentially problematic and eliminate compounds with inadequate solubility. In addition to the prediction of solubility from chemical structure, the interpretation of such models can give an insight into structure-solubility relationships and can guide the optimization of structures in order to provide better solubility whilst retaining the activity of the investigated drugs. Development of such models is a complex process that requires consideration of numerous factors which can impact the final model's performance. Different solubility modeling approaches are discussed in this article. Despite intensive research on model development, prediction of the solubility of diverse drugs remains a challenging task. The quality of available experimental data used for modeling of solubility is increasingly recognized as one of the main causes for the limited reliability of many of the proposed models. Therefore, the full potential of the developed modeling methods will only be achieved by greater availability of reliable data obtained by same experimental methodology.
AB  - Rastvorljivost leka u vodi je faktor koji može značajno da utiče na bioraspoloživost peroralno primenjenog leka, kao i na njegovu raspodelu u organizmu. Razmatranjem rastvorljivosti u ranim fazama otkrića i razvoja leka smanjuje se mogućnost neuspeha u daljem razvoju leka. Računarske metode za predviđanje rastvorljivosti lekova omogućavaju analizu kombinatornih baza podataka, identifikaciju potencijalno problematičnih jedinjenja i isključivanje onih čija je rastvorljivost neadekvatna. Pored predviđanja rastvorljivosti na osnovu hemijske strukture, analizom ovih modela moguće je detaljnije razjasniti odnose hemijske strukture i rastvorljivosti ispitivanih lekova i optimizovati strukture u cilju poboljšanja rastvorljivosti, pri čemu bi njihova aktivnost ostala nepromenjena. Razvoj ovakvih modela je kompleksan proces koji zahteva razmatranje velikog broja faktora koji mogu uticati na uspešnost predviđanja konačnog modela. U ovom radu su prikazani različiti pristupi koji se koriste u razvoju računarskih modela za predviđanje rastvorljivosti. I pored intenzivnog rada na razvoju ovih modela tokom protekle decenije, pouzdanost predviđanja rastvorljivosti lekova različitih struktura još uvek ostaje veliki izazov. Kvalitet dostupnih eksperimentalnih podataka koji se koriste u modelovanju rastvorljivosti se u sve većoj meri prepoznaje kao jedan od glavnih uzroka ograničene pouzdanosti većine do sada predloženih modela. Iskorišćenje punog potencijala razvijenih pristupa modelovanja rastvorljivosti uslovljeno je širom dostupnošću pouzdanih podataka za rastvorljivost određenih pod identičnim eksperimentalnim uslovima.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Computational models for the prediction of drug solubility
T1  - Računarski modeli za predviđanje rastvorljivosti lekova
VL  - 60
IS  - 4
SP  - 373
EP  - 390
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1446
ER  - 

@article{
author = "Erić, Slavica and Kalinić, Marko and Popović, Aleksandar",
year = "2010",
abstract = "Aqueous solubility of a drug is a factor which can significantly influence its oral bioavailability, and can also affect the drug distribution in the body. Consideration of aqueous solubility in early stages of drug discovery and development is vital in reducing the incidence of late-stage drug development failures. The application of computational models for solubility prediction could provide the screening of combinatorial libraries, helping single-out potentially problematic and eliminate compounds with inadequate solubility. In addition to the prediction of solubility from chemical structure, the interpretation of such models can give an insight into structure-solubility relationships and can guide the optimization of structures in order to provide better solubility whilst retaining the activity of the investigated drugs. Development of such models is a complex process that requires consideration of numerous factors which can impact the final model's performance. Different solubility modeling approaches are discussed in this article. Despite intensive research on model development, prediction of the solubility of diverse drugs remains a challenging task. The quality of available experimental data used for modeling of solubility is increasingly recognized as one of the main causes for the limited reliability of many of the proposed models. Therefore, the full potential of the developed modeling methods will only be achieved by greater availability of reliable data obtained by same experimental methodology., Rastvorljivost leka u vodi je faktor koji može značajno da utiče na bioraspoloživost peroralno primenjenog leka, kao i na njegovu raspodelu u organizmu. Razmatranjem rastvorljivosti u ranim fazama otkrića i razvoja leka smanjuje se mogućnost neuspeha u daljem razvoju leka. Računarske metode za predviđanje rastvorljivosti lekova omogućavaju analizu kombinatornih baza podataka, identifikaciju potencijalno problematičnih jedinjenja i isključivanje onih čija je rastvorljivost neadekvatna. Pored predviđanja rastvorljivosti na osnovu hemijske strukture, analizom ovih modela moguće je detaljnije razjasniti odnose hemijske strukture i rastvorljivosti ispitivanih lekova i optimizovati strukture u cilju poboljšanja rastvorljivosti, pri čemu bi njihova aktivnost ostala nepromenjena. Razvoj ovakvih modela je kompleksan proces koji zahteva razmatranje velikog broja faktora koji mogu uticati na uspešnost predviđanja konačnog modela. U ovom radu su prikazani različiti pristupi koji se koriste u razvoju računarskih modela za predviđanje rastvorljivosti. I pored intenzivnog rada na razvoju ovih modela tokom protekle decenije, pouzdanost predviđanja rastvorljivosti lekova različitih struktura još uvek ostaje veliki izazov. Kvalitet dostupnih eksperimentalnih podataka koji se koriste u modelovanju rastvorljivosti se u sve većoj meri prepoznaje kao jedan od glavnih uzroka ograničene pouzdanosti većine do sada predloženih modela. Iskorišćenje punog potencijala razvijenih pristupa modelovanja rastvorljivosti uslovljeno je širom dostupnošću pouzdanih podataka za rastvorljivost određenih pod identičnim eksperimentalnim uslovima.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Computational models for the prediction of drug solubility, Računarski modeli za predviđanje rastvorljivosti lekova",
volume = "60",
number = "4",
pages = "373-390",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1446"
}

Erić, S., Kalinić, M.,& Popović, A.. (2010). Computational models for the prediction of drug solubility. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 60(4), 373-390.
https://hdl.handle.net/21.15107/rcub_farfar_1446

Erić S, Kalinić M, Popović A. Computational models for the prediction of drug solubility. in Arhiv za farmaciju. 2010;60(4):373-390.
https://hdl.handle.net/21.15107/rcub_farfar_1446 .

Erić, Slavica, Kalinić, Marko, Popović, Aleksandar, "Computational models for the prediction of drug solubility" in Arhiv za farmaciju, 60, no. 4 (2010):373-390,
https://hdl.handle.net/21.15107/rcub_farfar_1446 .

TY  - JOUR
AU  - Erić, Slavica
AU  - Kalinić, Marko
AU  - Popović, Aleksandar
AU  - Makić, Halid
AU  - Civić, Elvisa
AU  - Bektašević, Mejra
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1425
AB  - Aqueous solubility is an important factor influencing several aspects of the pharmacokinetic profile of a drug. Numerous publications present different methodologies for the development of reliable computational models for the prediction of solubility from structure. The quality of such models can be significantly affected by the accuracy of the employed experimental solubility data. In this work, the importance of the accuracy of the experimental solubility data used for model training was investigated. Three data sets were used as training sets - data set 1, containing solubility data collected from various literature sources using a few criteria (n = 319), data set 2, created by substituting 28 values from data set 1 with uniformly determined experimental data from one laboratory (n = 319), and data set 3, created by including 56 additional components, for which the solubility was also determined under uniform conditions in the same laboratory, in the data set 2 (n = 375). The selection of the most significant descriptors was performed by the heuristic method, using one-parameter and multi-parameter analysis. The correlations between the most significant descriptors and solubility were established using multi-linear regression analysis (MLR) for all three investigated data sets. Notable differences were observed between the equations corresponding to different data sets, suggesting that models updated with new experimental data need to be additionally optimized. It was successfully shown that the inclusion of uniform experimental data consistently leads to an improvement in the correlation coefficients. These findings contribute to an emerging consensus that improving the reliability of solubility prediction requires the inclusion of many diverse compounds for which solubility was measured under standardized conditions in the data set.
AB  - Rastvorljivost leka u vodi je značajan faktor koji utiče na više aspekata njegovog farmakokinetičkog profila. Brojne publikacije prezentuju različite metodologije za razvoj pouzdanih kompjuterskih modela za predviđanje rastvorljivosti na osnovu strukture jedinjenja. Kvalitet modela za predviđanje rastvorljivosti bitno zavisi od tačnosti eksperimentalnih vrednosti za rastvorljivost koje su korišćene za treniranje modela. U ovom radu proučavan je značaj primene eksperimentalnih podataka dobijenih pod standardizovanim, uniformnim uslovima za treniranje modela za predviđanje rastvorljivosti. Korišćena su tri seta podataka - ispitivani set 1 koji je dobijen odabirom eksperimentalnih vrednosti za rastvorljivost pod određenim kriterijumima iz različitih literaturnih izvora (n = 319), zatim ispitivani set 2 koji je dobijen zamenom 28 vrednosti za rastvorljivost iz ispitivanog seta 1 vrednostima za rastvorljivost dobijenim standardizovanom eksperimentalnom metodom u jednoj laboratoriji (n = 319) i ispitivani set 3 koji je dobijen dodatkom još 56 komponenata u ispitivani set 2, za koje su vrednosti rastvorljivisti takođe određene pod standardizovanim uslovima u istoj laboratoriji (n = 375). Zatim je primenjena heuristička metoda za selekciju najznačajnijih deskriptora, korišćenjem jednoparametarskih i višeparametarskih analiza. Postavljene su korelacije između najznačajnijih deskriptora i rastvorljivosti korišćenjem multilinearne regresione analize za sva tri ispitivana seta podataka. Uočena je značajna razlika između jednačina koje su dobijene korišćenjem različitih setova podataka, što ukazuje na to da je nakon uvođenja novih eksperimentalnih podataka neophodno dodatno optimizovati postojeće modele. Pokazano je da korišćenje uniformnih eksperimentalnih podataka uslovljava poboljšanje koeficijenata korelacije. Ovi rezultati govore u prilog sve zastupljenijem stavu da je za poboljšanje pouzdanosti predviđanja rastvorljivosti potrebno koristiti setove podataka velikog broja različitih jedinjenja čija je rastvorljivost merena pod standardizovanim uslovima.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - The importance of the accuracy of the experimental data for the prediction of solubility
T1  - Važnost preciznosti eksperimentalnih podataka za procenu rastvorljivosti
VL  - 75
IS  - 4
SP  - 483
EP  - 495
DO  - 10.2298/JSC090809022E
ER  - 

@article{
author = "Erić, Slavica and Kalinić, Marko and Popović, Aleksandar and Makić, Halid and Civić, Elvisa and Bektašević, Mejra",
year = "2010",
abstract = "Aqueous solubility is an important factor influencing several aspects of the pharmacokinetic profile of a drug. Numerous publications present different methodologies for the development of reliable computational models for the prediction of solubility from structure. The quality of such models can be significantly affected by the accuracy of the employed experimental solubility data. In this work, the importance of the accuracy of the experimental solubility data used for model training was investigated. Three data sets were used as training sets - data set 1, containing solubility data collected from various literature sources using a few criteria (n = 319), data set 2, created by substituting 28 values from data set 1 with uniformly determined experimental data from one laboratory (n = 319), and data set 3, created by including 56 additional components, for which the solubility was also determined under uniform conditions in the same laboratory, in the data set 2 (n = 375). The selection of the most significant descriptors was performed by the heuristic method, using one-parameter and multi-parameter analysis. The correlations between the most significant descriptors and solubility were established using multi-linear regression analysis (MLR) for all three investigated data sets. Notable differences were observed between the equations corresponding to different data sets, suggesting that models updated with new experimental data need to be additionally optimized. It was successfully shown that the inclusion of uniform experimental data consistently leads to an improvement in the correlation coefficients. These findings contribute to an emerging consensus that improving the reliability of solubility prediction requires the inclusion of many diverse compounds for which solubility was measured under standardized conditions in the data set., Rastvorljivost leka u vodi je značajan faktor koji utiče na više aspekata njegovog farmakokinetičkog profila. Brojne publikacije prezentuju različite metodologije za razvoj pouzdanih kompjuterskih modela za predviđanje rastvorljivosti na osnovu strukture jedinjenja. Kvalitet modela za predviđanje rastvorljivosti bitno zavisi od tačnosti eksperimentalnih vrednosti za rastvorljivost koje su korišćene za treniranje modela. U ovom radu proučavan je značaj primene eksperimentalnih podataka dobijenih pod standardizovanim, uniformnim uslovima za treniranje modela za predviđanje rastvorljivosti. Korišćena su tri seta podataka - ispitivani set 1 koji je dobijen odabirom eksperimentalnih vrednosti za rastvorljivost pod određenim kriterijumima iz različitih literaturnih izvora (n = 319), zatim ispitivani set 2 koji je dobijen zamenom 28 vrednosti za rastvorljivost iz ispitivanog seta 1 vrednostima za rastvorljivost dobijenim standardizovanom eksperimentalnom metodom u jednoj laboratoriji (n = 319) i ispitivani set 3 koji je dobijen dodatkom još 56 komponenata u ispitivani set 2, za koje su vrednosti rastvorljivisti takođe određene pod standardizovanim uslovima u istoj laboratoriji (n = 375). Zatim je primenjena heuristička metoda za selekciju najznačajnijih deskriptora, korišćenjem jednoparametarskih i višeparametarskih analiza. Postavljene su korelacije između najznačajnijih deskriptora i rastvorljivosti korišćenjem multilinearne regresione analize za sva tri ispitivana seta podataka. Uočena je značajna razlika između jednačina koje su dobijene korišćenjem različitih setova podataka, što ukazuje na to da je nakon uvođenja novih eksperimentalnih podataka neophodno dodatno optimizovati postojeće modele. Pokazano je da korišćenje uniformnih eksperimentalnih podataka uslovljava poboljšanje koeficijenata korelacije. Ovi rezultati govore u prilog sve zastupljenijem stavu da je za poboljšanje pouzdanosti predviđanja rastvorljivosti potrebno koristiti setove podataka velikog broja različitih jedinjenja čija je rastvorljivost merena pod standardizovanim uslovima.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "The importance of the accuracy of the experimental data for the prediction of solubility, Važnost preciznosti eksperimentalnih podataka za procenu rastvorljivosti",
volume = "75",
number = "4",
pages = "483-495",
doi = "10.2298/JSC090809022E"
}

Erić, S., Kalinić, M., Popović, A., Makić, H., Civić, E.,& Bektašević, M.. (2010). The importance of the accuracy of the experimental data for the prediction of solubility. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 75(4), 483-495.
https://doi.org/10.2298/JSC090809022E

Erić S, Kalinić M, Popović A, Makić H, Civić E, Bektašević M. The importance of the accuracy of the experimental data for the prediction of solubility. in Journal of the Serbian Chemical Society. 2010;75(4):483-495.
doi:10.2298/JSC090809022E .

Erić, Slavica, Kalinić, Marko, Popović, Aleksandar, Makić, Halid, Civić, Elvisa, Bektašević, Mejra, "The importance of the accuracy of the experimental data for the prediction of solubility" in Journal of the Serbian Chemical Society, 75, no. 4 (2010):483-495,
https://doi.org/10.2298/JSC090809022E . .