期刊
DRUG DEVELOPMENT RESEARCH
卷 84, 期 3, 页码 514-526出版社
WILEY
DOI: 10.1002/ddr.22041
关键词
amphiphilic; antifungal; Cryptococcus neoformans; membrane disruption; synthesis
The limited availability of antifungal drugs has led to the necessity to develop new antifungals with different modes of action. Our investigation on a new series of peptides identified Boc-His-Trp-His[1-(4-tert-butylphenyl)] (10g) as the most promising inhibitor, exhibiting an IC50 value of 4.4 μg/mL against Cryptococcus neoformans. 10g showed high selectivity towards fungal cells and was nonhemolytic and noncytotoxic at its minimum inhibitory concentration. It exerted a fungicidal effect on growing cryptococcal cells and showed synergistic effect with amphotericin B.
Availability of a limited number of antifungal drugs created a necessity to develop new antifungals with distinct mode of action. Investigation on a new series of peptides led us to identify Boc-His-Trp-His[1-(4-tert-butylphenyl)] (10g) as the most promising inhibitor exhibiting IC50 value of 4.4 mu g/mL against Cryptococcus neoformans. Analog 10g exhibit high selectivity to fungal cells and was nonhemolytic and noncytotoxic at its minimum inhibitory concentration. 10g produced fungicidal effect on growing cryptococcal cells and displayed synergistic effect with amphotericin B. Overall cationic character of 10g resulted in interaction with negatively charged fungal membrane while hydrophobicity enhanced penetration inside the cryptococcal cells causing hole(s) formation and disruption to the membrane as evident by the scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy analyses. Flow cytometric investigation revealed rapid death of fungal cells by apopotic pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据