alexa Novel compounds targeting bacterial DNA topoisomerase DNA gyrase.


Organic Chemistry: Current Research

Author(s): Ehmann DE, Lahiri SD

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Abstract Among the targets for the development of new antibacterial agents, bacterial topoisomerases remain a vibrant area of discovery. A structurally diverse set of inhibitors that bind to the adenosine 5'-triphosphate (ATP) site of type II topoisomerases have been disclosed recently. Seven compounds with this mechanism are highlighted, focusing on antibacterial potency and spectrum, as well as examples of in vivo efficacy against pathogens including Staphylococcus aureus and Mycobacterium tuberculosis. Five compounds from two structural classes are exemplified that are inhibitors that bind to the catalytic site of DNA gyrase and topoisomerase IV. The pharmacokinetic and pharmacodynamic properties of these molecules, derived from in vivo efficacy against Gram-positive and Gram-negative pathogens, define the potential for these agents with broad-spectrum and targeted-spectrum clinical utilities. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved. This article was published in Curr Opin Pharmacol and referenced in Organic Chemistry: Current Research

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