Inhibition of 2,3-oxidosqualene-lanosterol cyclase in Candida albicans by pyridinium ion-based inhibitors

被引：17

作者：

Goldman, RC ^{[1
]}

Zakula, D ^{[1
]}

Capobianco, JO ^{[1
]}

Sharpe, BA ^{[1
]}

Griffin, JH ^{[1
]}

机构：

[1] STANFORD UNIV,DEPT CHEM,STANFORD,CA 94305

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 1996年 / 40卷 / 04期

关键词：

D O I：

10.1128/AAC.40.4.1044

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The N-(4E,8E)-5,9,13-trimethyl-4,8,12-tetradecatrien-1-ylpyridinium and N-(4E,8E)-5,9, 13-trimethyl-4,8,12-tetradecatrien-1-ylpicolinium cations were evaluated for their ability to inhibit 2,3-oxidosqualene-lanosterol cyclase activity in Candida albicans. Both compounds inhibited fungal growth, were fungicidal, and resulted in the accumulation of squalene epoxide concurrent with a decrease in ergosterol, monomethyl sterols, and lanosterol, as was expected for the specific inhibition of 2,3-oxidosqualene-lanosterol cyclase activity. These compounds are electron-poor aromatic mimics of a monocyclized transition state or high-energy intermediate formed from oxidosqualene, which may explain their selective action.

引用

页码：1044 / 1047

页数：4

共 28 条

[11] THE SQUALENE-2,3-EPOXIDE CYCLASE AS A MODEL FOR THE DEVELOPMENT OF NEW DRUGS [J].