TY  - JOUR
AU  - Mladenović, Milan
AU  - Mihailović, Mirjana
AU  - Bogojević, Desanka
AU  - Vuković, Nenad
AU  - Sukdolak, Slobodan
AU  - Matić, Sanja
AU  - Nićiforović, Neda
AU  - Mihailović, Vladimir
AU  - Mašković, Pavle
AU  - Vrvić, Miroslav M.
AU  - Solujić, Slavica
PY  - 2012
UR  - https://www.sciencedirect.com/science/article/pii/S0223523412002887?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3201
AB  - The objective of this study was to investigate in vitro and in vivo anticoagulant activity of sixteen 4-hydroxycoumarin derivatives bearing polar C-3 scaffolds. The activity was evaluated by measuring prothrombin time. Enhanced anticoagulant activity in vitro was observed for all tested compounds. Upon successive administration of 0.5 mg/kg of body weight to adult Wistar rats, over a period of five days, four derivatives (2b, 4c, 5c and 9c) presented anticoagulant activity in vivo. The most active compound was 2b, with PT = 30.0 s. Low or non-toxic effects in vivo were determined based on the catalytic activity of liver enzymes and the concentration of bilirubin, iron and proteins. Metabolic pathways of the most active compounds in vivo were determined after GC/MS analysis of collected rat urine samples. The excretion occurs by glucuronidation of 7-hydroxy forms of tested derivatives. In vivo results were described using PLS-based CoMFA and CoMSIA 3D-QSAR studies, which showed CoMFA-SE (q2 = 0.738) and CoMSIA-SEA (q2 = 0.763) to be the statistically most relevant models. Furthermore, molecular docking and DFT mechanistic studies performed on the rat VKORC1 homology model revealed interactions between the 4-OH coumarin group in the form of phenolic anion and the Cys135 catalytic site in the transition state.
T2  - European Journal of Medicinal Chemistry
T1  - Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants
VL  - 54
DO  - 10.1016/J.EJMECH.2012.04.036
SP  - 144
EP  - 158
ER  - 

@article{
author = "Mladenović, Milan and Mihailović, Mirjana and Bogojević, Desanka and Vuković, Nenad and Sukdolak, Slobodan and Matić, Sanja and Nićiforović, Neda and Mihailović, Vladimir and Mašković, Pavle and Vrvić, Miroslav M. and Solujić, Slavica",
year = "2012",
abstract = "The objective of this study was to investigate in vitro and in vivo anticoagulant activity of sixteen 4-hydroxycoumarin derivatives bearing polar C-3 scaffolds. The activity was evaluated by measuring prothrombin time. Enhanced anticoagulant activity in vitro was observed for all tested compounds. Upon successive administration of 0.5 mg/kg of body weight to adult Wistar rats, over a period of five days, four derivatives (2b, 4c, 5c and 9c) presented anticoagulant activity in vivo. The most active compound was 2b, with PT = 30.0 s. Low or non-toxic effects in vivo were determined based on the catalytic activity of liver enzymes and the concentration of bilirubin, iron and proteins. Metabolic pathways of the most active compounds in vivo were determined after GC/MS analysis of collected rat urine samples. The excretion occurs by glucuronidation of 7-hydroxy forms of tested derivatives. In vivo results were described using PLS-based CoMFA and CoMSIA 3D-QSAR studies, which showed CoMFA-SE (q2 = 0.738) and CoMSIA-SEA (q2 = 0.763) to be the statistically most relevant models. Furthermore, molecular docking and DFT mechanistic studies performed on the rat VKORC1 homology model revealed interactions between the 4-OH coumarin group in the form of phenolic anion and the Cys135 catalytic site in the transition state.",
journal = "European Journal of Medicinal Chemistry",
title = "Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants",
volume = "54",
doi = "10.1016/J.EJMECH.2012.04.036",
pages = "144-158"
}

Mladenović, M., Mihailović, M., Bogojević, D., Vuković, N., Sukdolak, S., Matić, S., Nićiforović, N., Mihailović, V., Mašković, P., Vrvić, M. M.,& Solujić, S.. (2012). Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants. in European Journal of Medicinal Chemistry, 54, 144-158.
https://doi.org/10.1016/J.EJMECH.2012.04.036

Mladenović M, Mihailović M, Bogojević D, Vuković N, Sukdolak S, Matić S, Nićiforović N, Mihailović V, Mašković P, Vrvić MM, Solujić S. Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants. in European Journal of Medicinal Chemistry. 2012;54:144-158.
doi:10.1016/J.EJMECH.2012.04.036 .

Mladenović, Milan, Mihailović, Mirjana, Bogojević, Desanka, Vuković, Nenad, Sukdolak, Slobodan, Matić, Sanja, Nićiforović, Neda, Mihailović, Vladimir, Mašković, Pavle, Vrvić, Miroslav M., Solujić, Slavica, "Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants" in European Journal of Medicinal Chemistry, 54 (2012):144-158,
https://doi.org/10.1016/J.EJMECH.2012.04.036 . .

TY  - JOUR
AU  - Mladenović, Milan
AU  - Mihailović, Mirjana
AU  - Bogojević, Desanka
AU  - Matić, Sanja
AU  - Nićiforović, Neda
AU  - Mihailović, Vladimir
AU  - Vuković, Nenad
AU  - Sukdolak, Slobodan
AU  - Solujić, Slavica
PY  - 2011
UR  - http://www.scopus.com/inward/record.url?eid=2-s2.0-79957795403&partnerID=tZOtx3y1
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3207
AB  - The series of fifteen synthesized 4-hydroxycoumarin derivatives was subjected to antioxidant activity evaluation in vitro, through total antioxidant capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl radical, lipid peroxide scavenging and chelating activity. The highest activity was detected during the radicals scavenging, with 2b, 6b, 2c, and 4c noticed as the most active. The antioxidant activity was further quantified by the quantitative structure-activity relationships (QSAR) studies. For this purpose, the structures were optimized using Paramethric Method 6 (PM6) semi-empirical and Density Functional Theory (DFT) B3LYP methods. Bond dissociation enthalpies of coumarin 4-OH, Natural Bond Orbital (NBO) gained hybridization of the oxygen, acidity of the hydrogen atom and various molecular descriptors obtained, were correlated with biological activity, after which we designed 20 new antioxidant structures, using the most favorable structural motifs, with much improved predicted activity in vitro.
T2  - International Journal of Molecular Sciences
T1  - In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies.
IS  - 5
VL  - 12
DO  - 10.3390/ijms12052822
SP  - 2822
EP  - 2841
ER  - 

@article{
author = "Mladenović, Milan and Mihailović, Mirjana and Bogojević, Desanka and Matić, Sanja and Nićiforović, Neda and Mihailović, Vladimir and Vuković, Nenad and Sukdolak, Slobodan and Solujić, Slavica",
year = "2011",
abstract = "The series of fifteen synthesized 4-hydroxycoumarin derivatives was subjected to antioxidant activity evaluation in vitro, through total antioxidant capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl radical, lipid peroxide scavenging and chelating activity. The highest activity was detected during the radicals scavenging, with 2b, 6b, 2c, and 4c noticed as the most active. The antioxidant activity was further quantified by the quantitative structure-activity relationships (QSAR) studies. For this purpose, the structures were optimized using Paramethric Method 6 (PM6) semi-empirical and Density Functional Theory (DFT) B3LYP methods. Bond dissociation enthalpies of coumarin 4-OH, Natural Bond Orbital (NBO) gained hybridization of the oxygen, acidity of the hydrogen atom and various molecular descriptors obtained, were correlated with biological activity, after which we designed 20 new antioxidant structures, using the most favorable structural motifs, with much improved predicted activity in vitro.",
journal = "International Journal of Molecular Sciences",
title = "In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies.",
number = "5",
volume = "12",
doi = "10.3390/ijms12052822",
pages = "2822-2841"
}

Mladenović, M., Mihailović, M., Bogojević, D., Matić, S., Nićiforović, N., Mihailović, V., Vuković, N., Sukdolak, S.,& Solujić, S.. (2011). In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies.. in International Journal of Molecular Sciences, 12(5), 2822-2841.
https://doi.org/10.3390/ijms12052822

Mladenović M, Mihailović M, Bogojević D, Matić S, Nićiforović N, Mihailović V, Vuković N, Sukdolak S, Solujić S. In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies.. in International Journal of Molecular Sciences. 2011;12(5):2822-2841.
doi:10.3390/ijms12052822 .

Mladenović, Milan, Mihailović, Mirjana, Bogojević, Desanka, Matić, Sanja, Nićiforović, Neda, Mihailović, Vladimir, Vuković, Nenad, Sukdolak, Slobodan, Solujić, Slavica, "In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies." in International Journal of Molecular Sciences, 12, no. 5 (2011):2822-2841,
https://doi.org/10.3390/ijms12052822 . .