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- W4309326802 abstract "Polymyxins are a class of lipopeptide anti-infective agents with potent and specific activity against Gram-negative bacteria. While toxicity concerns associated with polymyxin B and E (colistin) have historically limited their clinical application, today they are increasingly used as last-resort antibiotics given the rise of multidrug-resistant Gram-negative pathogens. The adverse side effects of polymyxins are well known, particularly as related to their nephrotoxicity. Here, we describe the synthesis and evaluation of a novel series of polymyxin analogues, aimed at reducing their nephrotoxic effects. Using a semisynthetic approach, we explored modifications of the exocyclic part of the polymyxin scaffold, namely, the terminal amino acid and lipophilic tail. By incorporating a reductively labile disulfide linkage in the lipid tail, we obtained novel polymyxins that exhibit potent antibacterial activity on par with polymyxin B but with reduced toxicity toward human renal proximal tubular epithelial cells." @default.
- W4309326802 created "2022-11-26" @default.
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- W4309326802 date "2022-11-18" @default.
- W4309326802 modified "2023-09-29" @default.
- W4309326802 title "Synthesis and Evaluation of Polymyxins Bearing Reductively Labile Disulfide-Linked Lipids" @default.
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- W4309326802 doi "https://doi.org/10.1021/acs.jmedchem.2c01528" @default.
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