Neomycin-phenolic conjugates: Polycationic amphiphiles with broad-spectrum antibacterial activity, low hemolytic activity and weak serum protein binding

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• 作者：Brandon Findlay^a ; George G. Zhanel^b ; Frank Schweizer^a ; ^b ; ^{schweize@ms.umanitoba.ca}
• 关键词：Aminoglycosides ; Quaternary ammonium chlorides ; Cationic amphiphiles ; Huisgen condensation ; Phenolic disinfectants
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：15 February, 2012
• 年：2012
• 卷：22
• 期：4
• 页码：1499-1503
• 全文大小：388 K

文摘

Here we present a proof-of-concept study, combining two known antimicrobial agents into a hybrid structure in order to develop an emergent cationic detergent-like interaction with the bacterial membrane. Six amphiphilic conjugates were prepared by copper (I)-catalyzed 1,3-dipolar cycloaddition between a neomycin B-derived azide and three alkyne-modified phenolic disinfectants. Three conjugates displayed good activity against a variety of clinically relevant Gram positive and Gram negative bacteria, including MRSA, without the high level of hemolysis or strong binding to serum proteins commonly observed with other cationic antimicrobial peptides and detergents.