Design, synthesis, and antifungal activities in vitro of novel tetrahydroisoquinoline compounds based on the structure of lanosterol 14α-demethylase (CYP51) of fungi

被引：49

作者：

Zhu, Ju ^{[1
]}

Lu, Jiaguo ^{[1
]}

Zhou, Youjun ^{[1
]}

Li, Yaowu ^{[1
]}

Cheng, Jun ^{[1
]}

Zheng, Canhui ^{[1
]}

机构：

[1] Second Mil Med Univ, Sch Pharm, Dept Med Chem, Shanghai 200433, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 20期

基金：

中国国家自然科学基金;

关键词：

CYP51; inhibitor; antifungal activity; tetrahydroisoquinoline; design; lanosterol 14 alpha-demethylase (CYP51);

D O I：

10.1016/j.bmcl.2006.08.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel tetrahydroisoquinoline compounds were designed by coupling structure-based de novo design based on the structure of lanosterol 14 alpha-demethylase (CYP51). The chemical synthesis and the antifungal activities in vitro of them were reported. The results exhibited that all of the lead compounds showed potent antifungal activities, in which compounds 6 and 7 had equal or stronger antifungal activities against five test fungi than that of fluconazole. The studies presented here provided the antifungal lead compounds. The affinity of the lead molecules for CYP51 was mainly attributed to their non-bonding interaction with the apoprotein, which was different from the azole antifungal agents. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5285 / 5289

页数：5