Structure-activity relationships of tetrahydrocarbazole derivatives as antifungal lead compounds

被引：16

作者：

Wang, Wenya ^{[2
,3
]}

Dong, Guoqiang ^{[2
]}

Gu, Julin ^{[1
,4
]}

Zhang, Yongqiang ^{[2
]}

Wang, Shengzheng ^{[2
]}

Zhu, Shiping ^{[2
]}

Liu, Yang ^{[2
]}

Miao, Zhenyuan ^{[2
]}

Yao, Jianzhong ^{[2
]}

Zhang, Wannian ^{[2
]}

Sheng, Chunquan ^{[2
]}

机构：

[1] Second Mil Med Univ, Changzheng Hosp, Dept Dermatol, Shanghai 20003, Peoples R China

[2] Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China

[3] Shanghai Inst Pharmaceut Ind, Novel Technol Ctr Pharmaceut Chem, Shanghai 200040, Peoples R China

[4] Second Mil Med Univ, Changzheng Hosp, Mycol Ctr, Shanghai 20003, Peoples R China

来源：

MEDCHEMCOMM | 2013年 / 4卷 / 02期

基金：

中国国家自然科学基金;

关键词：

ALBICANS N-MYRISTOYLTRANSFERASE; CRYSTAL-STRUCTURES; MOLECULAR DOCKING; AGENTS; INHIBITORS; BENZOFURANS; DESIGN; EPIDEMIOLOGY;

D O I：

10.1039/c2md20211e

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 Saccharomyces cerevisiae N-myristoyltransferase (NMT) inhibitor bearing a tetrahydrocarbazole scaffold was found to possess broad-spectrum antifungal activity. A series of C6- and N9-modified tetrahydrocarbazole derivatives were designed and synthesized. An in vitro antifungal assay indicated that several tetrahydrocarbazole derivatives showed improved activity with a broad spectrum. Particularly, the inhibitory activity of compound 10c against Cryptococcus neoformans, Aspergillus fumigatus and M. gypseum was comparable or superior to that of fluconazole and benzofuran NMT inhibitors. The present study provides a good starting point for the discovery of novel antifungal agents.

引用

页码：353 / 362

页数：10

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