Design of potent human steroid 5α-reductase inhibitors: 3D-QSAR CoMFA, CoMSIA and docking studies

被引：11

作者：

Kumar, Rajnish ^{[1
]}

Malla, Priyanka ^{[1
]}

Verma, Abhilasha ^{[1
]}

Kumar, Manoj ^{[1
]}

机构：

[1] Panjab Univ, Univ Inst Pharmaceut Sci, Chandigarh 160014, India

来源：

MEDICINAL CHEMISTRY RESEARCH | 2013年 / 22卷 / 10期

关键词：

5; alpha-Reductase; Docking; Dihydrotestosterone; CoMFA; CoMSIA; MOLECULAR-FIELD ANALYSIS; SIMILARITY INDEXES; DERIVATIVES; FINASTERIDE; BINDING; QSAR;

D O I：

10.1007/s00044-012-0456-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3D-QSAR CoMFA, CoMSIA and docking studies were performed on a set of 4-azasteroidal human steroid 5 alpha-reductase inhibitors. The models developed using maximal common substructure-based alignment was found to be reliable and significant with good predictive r (2) value. CoMSIA model developed using combination of steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor features has shown r (cv) (2) = 0.564 with six optimum components, r (ncv) (2) = 0.945, F value = 101.196, r (Pred) (2) = 0.693 and SEE = 0.209. The contour plots obtained has shown a favourable effect of bulkier groups at C-17 position. Docking studies indicates the importance of bulkier groups at C-17 position for favourable activity. The study further helps in design of potent inhibitors of the enzyme.

引用

页码：4568 / 4580

页数：13

共 30 条

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