期刊
LANGMUIR
卷 35, 期 16, 页码 5557-5567出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.9b00110
关键词
-
资金
- National Institutes of Health [R21 AI126053]
Small-molecule cationic amphiphiles (CAms) were designed to combat the rapid rise in drug-resistant bacteria. CAms were designed to target and compromise the structural integrity of bacteria membranes, leading to cell rupture and death. Discrete structural features of CAms were varied, and structure-activity relationship studies were performed to guide the rational design of potent antimicrobials with desirable selectivity and cytocompatibility profiles. In particular, the effects of cationic conformational flexibility, hydrophobic domain flexibility, and hydrophobic domain architecture were evaluated. Their influence on antimicrobial efficacy in Gram-positive and Gram-negative bacteria was determined, and their safety profiles were established by assessing their impact on mammalian cells. All CAms have a potent activity against bacteria, and hydrophobic domain rigidity and branched architecture contribute to specificity. The insights gained from this project will aid in the optimization of CAm structures.
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