Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: anti-Mycobacterium tuberculosis activity and cytotoxicity

Eur J Med Chem. 2010 May;45(5):1898-905. doi: 10.1016/j.ejmech.2010.01.028. Epub 2010 Jan 28.

Abstract

The aim of this study was to identify a candidate drug for the development of anti-tuberculosis therapy from previously synthesized compounds based on the thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones compounds. The minimal inhibitory concentration (MIC) of these compounds against Mycobacterium tuberculosis was determined. Their in vitro cytotoxicity to J774 cells (IC50) was determined to establish a selectivity index (SI) (SI=IC50/MIC). The best compounds were the thiosemicarbazones (2, 3 and 4) and the hydrazide/hydrazones (14, 15, 16 and 18). The results are comparable to or better than those of "first line" or "second line" drugs commonly used to treat TB, suggesting these compounds as anti-TB drug candidates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Hydrazines / chemical synthesis
  • Hydrazines / chemistry
  • Hydrazines / pharmacology*
  • Mice
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / metabolism
  • Semicarbazones / chemical synthesis
  • Semicarbazones / chemistry
  • Semicarbazones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antitubercular Agents
  • Hydrazines
  • Semicarbazones