Antibiotics, Volume 13, Issue 1
January 2024 - 109 articles
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Cover Story: Colistin is used as a last-resort antibiotic against highly resistant Gram-negative bacteria (GNB). Rising rates of colistin resistance, however, may limit future use of this agent. The anthelmintic drug niclosamide has been shown to enhance colistin activity in combination therapy, but a detailed structure–activity relationship (SAR) for niclosamide against GNB has yet to be studied. A series of niclosamide analogs were synthesized to perform an SAR, leading to the discovery of a lead compound that displayed comparable colistin-potentiating activity to niclosamide with reduced cytotoxicity. Overall, this work provides important insights into synthetic strategies for the future development of novel niclosamide derivatives and demonstrates that toxicity to mammalian cells can be reduced while maintaining colistin potentiation. View this paper