Bioorganic & Medicinal Chemistry Letters 2010-06-15

Biological activity of modified and exchanged 2-amino-5-nitrothiazole amide analogues of nitazoxanide.

T Eric Ballard, Xia Wang, Igor Olekhnovich, Taylor Koerner, Craig Seymour, Paul S Hoffman, Timothy L Macdonald

Index: Bioorg. Med. Chem. Lett. 20(12) , 3537-9, (2010)

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Abstract

Head group analogues of the antibacterial and antiparasitic drug nitazoxanide (NTZ) are presented. A library of 39 analogues was synthesized and assayed for their ability to suppress growth of Helicobacter pylori, Campylobacter jejuni, Clostridium difficile and inhibit NTZ target pyruvate:ferredoxin oxidoreductase (PFOR). Two head groups assayed recapitulated NTZ activity and possessed improved activity over their 2-amino-5-nitrothiazole counterparts, demonstrating that head group modification is a viable route for the synthesis of NTZ-related antibacterial analogues.Copyright 2010 Elsevier Ltd. All rights reserved.