Discovery and in vivo evaluation of alcohol-containing benzothiazoles as potent dual-targeting bacterial DNA supercoiling inhibitors.

Abstract

A series of dual-targeting, alcohol-containing benzothiazoles has been identified with superior antibacterial activity and drug-like properties. Early lead benzothiazoles containing carboxylic acid moieties showed efficacy in a well-established in vivo model, but inferior drug-like properties demanded modifications of functionality capable of demonstrating superior efficacy. Eliminating the acid group in favor of hydrophilic alcohol moieties at C(5), as well as incorporating solubilizing groups at the C(7) position of the core ring provided potent, broad-spectrum Gram-positive antibacterial activity, lower protein binding, and markedly improved efficacy in vivo.

DOI: 10.1016/j.bmcl.2014.07.037

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Cite this paper

@article{Palmer2014DiscoveryAI, title={Discovery and in vivo evaluation of alcohol-containing benzothiazoles as potent dual-targeting bacterial DNA supercoiling inhibitors.}, author={James T Palmer and Lorraine C Axford and Stephanie Barker and James Michael Bennett and Michael Blair and Ian Collins and D. T. P. Davies and Leigh Ford and Carlie T Gannon and Paul Lancett and Alastair Logan and Christopher J Lunniss and Craig J. Morton and Daniel A Offermann and Gary R W Pitt and B . Narasinga Rao and Amit K. Singh and Tarun Shukla and Anil Srivastava and Neil R. Stokes and Helena B. Thomaides-Brears and Anju Yadav and David J. Haydon}, journal={Bioorganic & medicinal chemistry letters}, year={2014}, volume={24 17}, pages={4215-22} }