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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Ballard, T. Eric¹  Wang, Xia²  Olekhnovich, Igor²  Koerner, Taylor¹  Seymour, Craig¹  Hoffman, Paul S.^2,3  Macdonald, Timothy L.¹ 

[1] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA

[2] Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA

[3] Univ Virginia, Sch Med, Dept Microbiol, Charlottesville, VA 22908 USA

关键词: Nitazoxanide;    Antibacterial;    Small-molecule drug target;    Pyruvate:ferredoxin oxidoreductase;    Helicobacter pylori;    Campylobacter jejuni;    Clostridium difficile;   

DOI  :  10.1016/j.bmcl.2010.04.126

来源: Elsevier

【 摘 要 】

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. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

Free