4.4 Article

Synthetic amino acids-based short amphipathic peptides exhibit antifungal activity by targeting cell membrane disruption

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

向作者/读者索取更多资源

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。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据