Molecular docking and QSAR study on imidazole derivatives as 14  /alpha -demethylase inhibitors

Asghar DAVOOD; Maryam IMAN

Makale detayları

Molecular docking and QSAR study on imidazole derivatives as 14 /alpha -demethylase inhibitors

Yazarlar:

Asghar DAVOOD | Maryam IMAN

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Chemistry 2013 Vol.37 Issue 1, pp.119-133

Belge Tipi:

Makale

Yayın Tarihi:

12/2012

Belge Dili:

Türkçe

Document ID (Org No.):

2000727499

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527

Özet:

 

14a-Demethylase (CYP51) inhibitors have been widely  used in the treatment of fungal infections.  In this study, a series  of imidazole derivatives with CYP51 inhibitory activity were subjected to a molecular docking study followed by quantitative  structure-activity relationship (QSAR) analyses in search of the  ideal physicochemical characteristics of potential CYP51 inhibitors.  Desired imidazoles were built using the HyperChem program, and  conformational studies were performed through a semiempirical method  followed by the PM3 method.  Docking study was performed using the  AutoDock program on all of the compounds.  Different QSAR descriptors were calculated using DRAGON, AutoDock, and HyperChem.  Multilinear regression was used as a chemometric tool for QSAR modeling.  The docking study indicated that all of compounds 1-43 interact with the 14a-demethylase, and azole-heme coordination and p-p and p-cation interactions are involved in drug-receptor interaction.  In the p-p and p-cation interactions, the aryl moieties interact with Phe 255 and Arg 96, and the role of the phenoxy group is more important than that of the phenyl group.The developed QSAR model indicated the importance of atomic van der Waals volumes and atomic Sanderson electronegativities.  The sums of the R6u, RDF030v, Mor25v, GATs5e, and R5e+ were identified as the most significant descriptors.  The developed QSAR model was statistically significant according to the validation parameters.

 

14a-Demethylase (CYP51) inhibitors have been widely  used in the treatment of fungal infections.  In this study, a series  of imidazole derivatives with CYP51 inhibitory activity were subjected to a molecular docking study followed by quantitative  structure-activity relationship (QSAR) analyses in search of the  ideal physicochemical characteristics of potential CYP51 inhibitors.  Desired imidazoles were built using the HyperChem program, and  conformational studies were performed through a semiempirical method  followed by the PM3 method.  Docking study was performed using the  AutoDock program on all of the compounds.  Different QSAR descriptors were calculated using DRAGON, AutoDock, and HyperChem.  Multilinear regression was used as a chemometric tool for QSAR modeling.  The docking study indicated that all of compounds 1-43 interact with the 14a-demethylase, and azole-heme coordination and p-p and p-cation interactions are involved in drug-receptor interaction.  In the p-p and p-cation interactions, the aryl moieties interact with Phe 255 and Arg 96, and the role of the phenoxy group is more important than that of the phenyl group.The developed QSAR model indicated the importance of atomic van der Waals volumes and atomic Sanderson electronegativities.  The sums of the R6u, RDF030v, Mor25v, GATs5e, and R5e+ were identified as the most significant descriptors.  The developed QSAR model was statistically significant according to the validation parameters.

Makale detayları

Molecular docking and QSAR study on imidazole derivatives as 14 /alpha -demethylase inhibitors

Yazarlar: Asghar DAVOOD | Maryam IMAN

Yayıncı: TUBITAK

Dergi: Turkish Journal of Chemistry 2013 Vol.37 Issue 1, pp.119-133

Belge Tipi: Makale

Yayın Tarihi: 12/2012

Belge Dili: Türkçe

Document ID (Org No.): 2000727499

Sıklık: İki Aylık

eISSN: 1303-6130

pISSN: 1300-0527

Sayı

Yazarlar:

Asghar DAVOOD | Maryam IMAN

Yayıncı:

TUBITAK

Dergi:

Turkish Journal of Chemistry 2013 Vol.37 Issue 1, pp.119-133

Belge Tipi:

Makale

Yayın Tarihi:

12/2012

Belge Dili:

Türkçe

Document ID (Org No.):

2000727499

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527