Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as-adrenoceptor antagonists.
10.1016/j.apsb.2017.04.011
- Author:
Wei XU
1
;
Junjun HUANG
2
;
Renwang JIANG
1
;
Mu YUAN
2
Author Information
1. College of Pharmacy, Jinan University, Guangzhou 510632, China.
2. Pharmaceutical Research Center, Guangzhou Medical University, Guangzhou 510182, China.
- Publication Type:Journal Article
- Keywords:
Binding mode;
Crystal structure;
Naftopidil;
Pharmacophore model;
α1D-Adrenoceptor antago- nists
- From:
Acta Pharmaceutica Sinica B
2017;7(4):496-501
- CountryChina
- Language:English
-
Abstract:
Chiral drug naftopidil (NAF), a specific-adrenoceptor (AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the-AR, but the binding mechanism of these two stereochemical NAF isomers to thereceptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data ofandenantiomers matched satisfactorily the pharmacophore model for-selective antagonists. Based on the constructedhomology model, molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.
