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Synthesis and Antimycobacterial Activity of Some New Pyrazinamide Derivatives

Some pyrazinamide derivatives (2a-2e, 2a′-2e′, and 2a″-2e″) were synthesized and evaluated as antimycobacterial agents against Mycobacterium tuberculosis H37Rv strain. These derivatives were designed by structural modification of pyrazinamide with alkyl chains and six-membered hetereocylic rings, respectively. The title compounds were synthesized using pyrazinamide as the starting material for haloakylation (1a-1c), and then halo-alkylpyrazinamides were reacted with appropriate heterocyclic rings. The structures of compounds were confirmed by 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. The activity of pyrazinamide derivatives was assayed using microplate alamar blue assay (MABA) and characterized by minimum inhibitory concentrations (MICs). Results showed that the obtained pyrazinamide derivatives exhibited high inhibitory effect on M. tuberculosis. The antimycobacterial activity of compounds 2b′, 2d′, and 2e′ was the best among all compounds tested, and their MIC values were about 6.25 mμ/mL. These compounds have ethylene chain between pyrazinamide moiety and six-membered hetereocylic rings.

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The authors declare that they have no conflicts of interest.

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Correspondence to Mohammad Asif.

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Almehmadi, M., Halawi, M. & Asif, M. Synthesis and Antimycobacterial Activity of Some New Pyrazinamide Derivatives. Pharm Chem J 56, 456–460 (2022). https://doi.org/10.1007/s11094-022-02662-7

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  • DOI: https://doi.org/10.1007/s11094-022-02662-7

Keywords

  • pyrazinamide derivatives
  • synthesis
  • antimycobacterial activity
  • heterocyclic rings