Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as -adrenoceptor antagonists.

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 the receptor 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 of and enantiomers matched satisfactorily the pharmacophore model for -selective antagonists. Based on the constructed homology 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.