Activity of megazol, a trypanocidal nitroimidazole, is associated with DNA damage

Antimicrob Agents Chemother. 2003 Oct;47(10):3368-70. doi: 10.1128/AAC.47.10.3368-3370.2003.

Abstract

DNA damage associated with the trypanocidal activity of megazol [2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole] was shown in experiments in which DNA repair-deficient RAD51(-/-) Trypanosoma brucei mutants were found to be hypersensitive to the drug. Parasites resistant to megazol were selected and showed modest cross-resistance to other trypanocides, although neither drug efflux nor changes to intracellular thiols correlated with resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Damage*
  • DNA-Binding Proteins / genetics
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Multiple / genetics
  • Inhibitory Concentration 50
  • Mutation
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei brucei / drug effects
  • Trypanosoma brucei brucei / genetics

Substances

  • DNA-Binding Proteins
  • Thiadiazoles
  • Trypanocidal Agents
  • megazol