title: Biological activity of modified and exchanged 2-amino-5-nitrothiazole amide analogues of nitazoxanide.
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.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, VA 22904-4319, USA. teb2m@virginia.edu
authors.forename: T Eric
authors.initials: TE
authors.lastname: Ballard
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Igor
authors.initials: I
authors.lastname: Olekhnovich
authors.forename: Taylor
authors.initials: T
authors.lastname: Koerner
authors.forename: Craig
authors.initials: C
authors.lastname: Seymour
authors.forename: Paul S
authors.initials: PS
authors.lastname: Hoffman
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Macdonald
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016123:Campylobacter jejuni / Q000187:drug effects; D016360:Clostridioides difficile / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects; D009574:Nitro Compounds; D050743:Pyruvate Synthase / Q000037:antagonists & inhibitors; D054852:Small Molecule Libraries / Q000138:chemical synthesis; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000977:Antiparasitic Agents; D009574:Nitro Compounds; D054852:Small Molecule Libraries; D013844:Thiazoles; C034870:2-amino-5-nitrothiazole; D050743:Pyruvate Synthase; C041747:nitazoxanide