TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Marković, Bojan
AU  - Milenković, Nikola
AU  - Savić, Vladimir
AU  - Jaćević, Vesna
AU  - Rancić, Nemanja
AU  - Vladimirov, Sote
AU  - Čudina, Olivera
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2132
AB  - Molecular docking studies were performed on 18 17-carboxamide steroids in order to select compounds with potential local anti-inflammatory activity. These derivatives are amides of cortienic acids (obtained from hydrocortisone, prednisolone, and methylprednisolone) with methyl or ethyl esters of six amino acids. Interactions with the glucocorticoid receptor (GR), binding energies and ligand efficiency values of these compounds were compared with dexamethasone and cortienic acid obtained from prednisolone (inactive metabolite). On the basis of molecular docking studies, seven compounds were selected and their binding affinities for the GR were predicted by use of the exponential model created in this study. Subsequently, selected compounds were synthesized in good yields by use of modified N,N-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) coupling procedure. Finally, the local anti-inflammatory activity of the synthesized compounds was examined by use of the croton oil-induced ear edema test. In vivo evaluation of systemic side effects as well as in silico prediction of metabolism were performed on the derivative with the best local anti-inflammatory activity. The combination of molecular docking studies and the exponential model for the GR binding affinity prediction could be used as an in silico tool for the rational design of novel 17-carboxamide steroids with potentially better biological profile than dexamethasone.
PB  - Wiley-VCH Verlag GMBH, Weinheim
T2  - Archiv der Pharmazie
T1  - Design, Synthesis, and Local Anti-Inflammatory Activity of 17 beta-Carboxamide Derivatives of Glucocorticoids
VL  - 347
IS  - 11
SP  - 786
EP  - 797
DO  - 10.1002/ardp.201400165
ER  - 

@article{
author = "Dobričić, Vladimir and Marković, Bojan and Milenković, Nikola and Savić, Vladimir and Jaćević, Vesna and Rancić, Nemanja and Vladimirov, Sote and Čudina, Olivera",
year = "2014",
abstract = "Molecular docking studies were performed on 18 17-carboxamide steroids in order to select compounds with potential local anti-inflammatory activity. These derivatives are amides of cortienic acids (obtained from hydrocortisone, prednisolone, and methylprednisolone) with methyl or ethyl esters of six amino acids. Interactions with the glucocorticoid receptor (GR), binding energies and ligand efficiency values of these compounds were compared with dexamethasone and cortienic acid obtained from prednisolone (inactive metabolite). On the basis of molecular docking studies, seven compounds were selected and their binding affinities for the GR were predicted by use of the exponential model created in this study. Subsequently, selected compounds were synthesized in good yields by use of modified N,N-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) coupling procedure. Finally, the local anti-inflammatory activity of the synthesized compounds was examined by use of the croton oil-induced ear edema test. In vivo evaluation of systemic side effects as well as in silico prediction of metabolism were performed on the derivative with the best local anti-inflammatory activity. The combination of molecular docking studies and the exponential model for the GR binding affinity prediction could be used as an in silico tool for the rational design of novel 17-carboxamide steroids with potentially better biological profile than dexamethasone.",
publisher = "Wiley-VCH Verlag GMBH, Weinheim",
journal = "Archiv der Pharmazie",
title = "Design, Synthesis, and Local Anti-Inflammatory Activity of 17 beta-Carboxamide Derivatives of Glucocorticoids",
volume = "347",
number = "11",
pages = "786-797",
doi = "10.1002/ardp.201400165"
}

Dobričić, V., Marković, B., Milenković, N., Savić, V., Jaćević, V., Rancić, N., Vladimirov, S.,& Čudina, O.. (2014). Design, Synthesis, and Local Anti-Inflammatory Activity of 17 beta-Carboxamide Derivatives of Glucocorticoids. in Archiv der Pharmazie
Wiley-VCH Verlag GMBH, Weinheim., 347(11), 786-797.
https://doi.org/10.1002/ardp.201400165

Dobričić V, Marković B, Milenković N, Savić V, Jaćević V, Rancić N, Vladimirov S, Čudina O. Design, Synthesis, and Local Anti-Inflammatory Activity of 17 beta-Carboxamide Derivatives of Glucocorticoids. in Archiv der Pharmazie. 2014;347(11):786-797.
doi:10.1002/ardp.201400165 .

Dobričić, Vladimir, Marković, Bojan, Milenković, Nikola, Savić, Vladimir, Jaćević, Vesna, Rancić, Nemanja, Vladimirov, Sote, Čudina, Olivera, "Design, Synthesis, and Local Anti-Inflammatory Activity of 17 beta-Carboxamide Derivatives of Glucocorticoids" in Archiv der Pharmazie, 347, no. 11 (2014):786-797,
https://doi.org/10.1002/ardp.201400165 . .