Antimicrobial Lexitropsins Containing Amide, Amidine, and Alkene Linking Groups

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• 作者：Nahoum G. Anthony ; David Breen ; Joanna Clarke ; Gavin Donoghue ; Allan J. Drummond ; Elizabeth M. Ellis ; Curtis G. Gemmell ; Jean-Jacques Helesbeux ; Iain S. Hunter ; Abedawn I. Khalaf ; Simon P. Mackay ; Joh
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 29, 2007
• 年：2007
• 卷：50
• 期：24
• 页码：6116 - 6125
• 全文大小：315K
• 年卷期：v.50,no.24(November 29, 2007)
• ISSN：1520-4804

文摘

The synthesis and properties of 80 short minor groove binders related to distamycin and the thiazotropsinsare described. The design of the compounds was principally predicated upon increased affinity arising fromhydrophobic interactions between minor groove binders and DNA. The introduction of hydrophobic aromatichead groups, including quinolyl and benzoyl derivatives, and of alkenes as linkers led to several stronglyactive antibacterial compounds with MIC for Staphylococcus aureus, both methicillin-sensitive and -resistantstrains, in the range of 0.1-5 g mL^-1, which is comparable to many established antibacterial agents.Antifungal activity was also found in the range of 20-50 g mL^-1 MIC against Aspergillus niger andCandida albicans, again comparable with established antifungal drugs. A quinoline derivative was found toprotect mice against S. aureus infection for a period of up to six days after a single intraperitoneal dose of40 mg kg^-1.