Synthesis and in vitro antitubercular activity of some 1-[(4-sub)phenyl]-3-(4-{1-[(pyridine-4-carbonyl)hydrazono]ethyl}phenyl)thiourea

Bioorg Med Chem Lett. 2006 Feb 15;16(4):876-8. doi: 10.1016/j.bmcl.2005.11.004. Epub 2005 Nov 21.

Abstract

Various isonicotinyl hydrazones were prepared by reacting isonicotinyl hydrazide [INH] with 1-(4-acetylphenyl)-3-[(4-sub)phenyl]thiourea and were tested for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv and INH-resistant M. tuberculosis using the BACTEC 460 radiometric system. Among the synthesized compounds, 1-(4-fluorophenyl)-3-(4-{1-[(pyridine-4-carbonyl)-hydrazono]ethyl}phenyl)thiourea (4d) was found to be the most potent compound with a minimum inhibitory concentration of 0.49 microM against M. tuberculosis H37Rv and INH-resistant M. tuberculosis. When compared to INH, 4d was found to be 3 and 185 times more active against M. tuberculosis H37Rv and INH-resistant M. tuberculosis, respectively, with a selectivity index of >300.

MeSH terms

  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Drug Resistance, Bacterial
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Phenylthiourea / analogs & derivatives*
  • Phenylthiourea / chemical synthesis
  • Phenylthiourea / chemistry
  • Phenylthiourea / pharmacology
  • Structure-Activity Relationship

Substances

  • 1-(4-fluorophenyl)-3-(4-(1-((pyridine-4-carbonyl)hydrazono)ethyl)phenyl)thiourea
  • Antitubercular Agents
  • Phenylthiourea