Thiazolides as novel antiviral agents. 1. Inhibition of hepatitis B virus replication

Andrew V Stachulski, Chandrakala Pidathala, Eleanor C Row, Raman Sharma, Neil G Berry, Mazhar Iqbal, Joanne Bentley, Sarah A Allman, Geoffrey Edwards, Alison Helm, Jennifer Hellier, Brent E Korba, J Edward Semple, Jean-Francois Rossignol

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


We report the syntheses and activities of a wide range of thiazolides [viz., 2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis B virus replication, with QSAR analysis of our results. The prototypical thiazolide, nitazoxanide [2-hydroxybenzoyl-N-(5-nitrothiazol-2-yl)amide, NTZ] 1 is a broad spectrum antiinfective agent effective against anaerobic bacteria, viruses, and parasites. By contrast, 2-hydroxybenzoyl-N-(5-chlorothiazol-2-yl)amide 3 is a novel, potent, and selective inhibitor of hepatitis B replication (EC(50) = 0.33 μm) but is inactive against anaerobes. Several 4'- and 5'-substituted thiazolides show good activity against HBV; by contrast, some related salicyloylanilides show a narrower spectrum of activity. The ADME properties of 3 are similar to 1; viz., the O-acetate is an effective prodrug, and the O-aryl glucuronide is a major metabolite. The QSAR study shows a good correlation of observed EC(90) for intracellular virions with thiazolide structural parameters. Finally we discuss the mechanism of action of thiazolides in relation to the present results.
Original languageEnglish
Article numberN/A
Pages (from-to)4119-4132
Number of pages14
JournalJournal of Medicinal Chemistry
Issue number12
Publication statusPublished - 23 Jun 2011


  • Amides
  • Animals
  • Antiviral Agents
  • Dogs
  • Glucuronides
  • Hep G2 Cells
  • Hepatitis B virus
  • Humans
  • Prodrugs
  • Quantitative Structure-Activity Relationship
  • Rats
  • Salicylamides
  • Thiazoles
  • Virion
  • Virus Replication


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