From Triclosan toward the Clinic: Discovery of Nonbiocidal, Potent FabI Inhibitors for the Treatment of Resistant Bacteria

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• 作者：Vincent Gerusz ; Alexis Denis ; Fabien Faivre ; Yannick Bonvin ; Mayalen Oxoby ; Sophia Briet ; G茅raldine LeFralliec ; Chrystelle Oliveira ; Nicolas Desroy ; C茅dric Raymond ; La毛titia Peltier ; Fran莽ois Moreau ; Sonia Escaich ; Vanida Vongsouthi ; St茅phanie Floquet ; Elodie Drocourt ; Armelle Walton ; Laure Prouvensier ; Marc Saccomani ; Lionel Durant ; Jean-Marie Genevard ; Vanessa Sam-Sambo ; Coralie Soulama-Mouze
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：November 26, 2012
• 年：2012
• 卷：55
• 期：22
• 页码：9914-9928
• 全文大小：608K
• 年卷期：v.55,no.22(November 26, 2012)
• ISSN：1520-4804

文摘

In this paper, we present some elements of our optimization program to decouple triclosan鈥檚 specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.