A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study

被引：5

作者：

Al-Masoudi, Najim A. ^{[1
]}

Mahdi, Kuthiar M. ^{[2
]}

Abdul-Rida, Nabeel A. ^{[2
]}

Saeed, Bahjat A. ^{[3
]}

Engel, Mathias ^{[4
]}

机构：

[1] Univ Basrah, Coll Sci, Dept Chem, Basrah, Iraq

[2] Univ Qadisiya, Coll Educ, Dept Chem, Qadisiya, Iraq

[3] Univ Basrah, Coll Educ, Dept Chem, Basrah, Iraq

[4] Univ Saarland, Inst Pharmazeut & Med Chem, D-81310 Saarbrucken, Germany

来源：

STEROIDS | 2015年 / 100卷

关键词：

CYP17; hydroxylase; Imine analogues; Molecular docking; Pregnenolone; Prostate cancer; PROSTATE-CANCER; BIOLOGICAL EVALUATION; ABIRATERONE ACETATE; ANTITUMOR-ACTIVITY; CYP-17; INHIBITORS; AGENTS; PHARMACOKINETICS; P450(17-ALPHA); SUBSTITUTION; DERIVATIVES;

D O I：

10.1016/j.steroids.2015.05.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new series of 17-(N-(arylimino)-5-pregnen-3 beta-ol derivatives 19-32 as well as carboxylate and acrylate analogues of pregnenolone 37-40 were synthesized and evaluated for their inhibitory activity against human CYP17 hydroxylase expressed in Escherichia coli. Compounds 32 and 37 were the Most potent analogues in this series, showing inhibition activity with IC50 = 2.11 and 1.29 mu M, respectively. However, the analogue 37 revealed a better selectivity profile (83.21% inhibition of hydroxylase), which is a leading candidate for further development. Molecular docking study of 37 showed binding with the amino acid residues of CYP17 through hydrogen bonds and hydrophobic interaction. (C) 2015 Published by Elsevier Inc.

引用

页码：52 / 59

页数：8

共 38 条

[1]

Akram SMM, 2013, J ADV CHEM, V5, P626

[2] New CYP17 Hydroxylase Inhibitors: Synthesis, Biological Evaluation, QSAR, and Molecular Docking Study of New Pregnenolone Analogs [J].