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

James T Palmer, Lorraine C. Axford, Stephanie Barker, James M. Bennett, Michael Blair, Ian Collins, David T. Davies, Leigh Ford, Carlie T. Gannon, Paul Lancett, Alastair Logan, Christopher J. Lunniss, Craig J. Morton, Daniel A. Offermann, Gary R W Pitt, B. Narasinga Rao, Amit K. Singh, Tarun Shukla, Anil Srivastava, Neil R. StokesHelena B. Thomaides-Brears, Anju Yadav, David J. Haydon

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14 Citations (Scopus)


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 C7 position of the core ring provided potent, broad-spectrum Gram-positive antibacterial activity, lower protein binding, and markedly improved efficacy in vivo.

Original languageEnglish
Pages (from-to)4215-4222
Number of pages8
JournalBioorganic and Medicinal Chemistry Letters
Issue number17
Publication statusPublished - 1 Sep 2014
Externally publishedYes


  • Antibacterial
  • DNA gyrase
  • Dual-targeting
  • In vivo
  • Synthesis
  • Topoisomerase

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