Synthesis and antimycobacterial activity of new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives

Bioorg Med Chem. 2003 May 15;11(10):2149-56. doi: 10.1016/s0968-0896(03)00119-6.

Abstract

As a continuation of our research and with the aim of obtaining new antituberculosis agents which can improve the current chemotherapeutic antituberculosis treatments, new series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis strain H(37)Rv, using the radiometric BACTEC 460-TB methodology. Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. The results indicate that some compounds exhibited a good antituberculosis activity and the arylcarboxamide analogues 3, 8, and 9 were the most active compounds (EC(90)/MIC1). Also, the cytotoxic effects indicate that these compounds have a good Selectivity Index (SI).

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / toxicity
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Macrophages / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Nitriles / chemical synthesis*
  • Nitriles / pharmacology
  • Nitriles / toxicity
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / pharmacology
  • Quinoxalines / toxicity
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Antitubercular Agents
  • Nitriles
  • Quinoxalines
  • quinoxaline-2-carbonitrile 1,4-di-N-oxide