Pharmaceuticals (Aug 2021)

Synthesis, Biological Evaluation, and In Silico Modeling of <i>N</i>-Substituted Quinoxaline-2-Carboxamides

  • Ghada Bouz,
  • Sarah Bouz,
  • Ondřej Janďourek,
  • Klára Konečná,
  • Pavel Bárta,
  • Jarmila Vinšová,
  • Martin Doležal,
  • Jan Zitko

DOI
https://doi.org/10.3390/ph14080768
Journal volume & issue
Vol. 14, no. 8
p. 768

Abstract

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Despite the established treatment regimens, tuberculosis remains an alarming threat to public health according to WHO. Novel agents are needed to overcome the increasing rate of resistance and perhaps achieve eradication. As part of our long-term research on pyrazine derived compounds, we prepared a series of their ortho fused derivatives, N-phenyl- and N-benzyl quinoxaline-2-carboxamides, and evaluated their in vitro antimycobacterial activity. In vitro activity against Mycobacterium tuberculosis H37Ra (represented by minimum inhibitory concentration, MIC) ranged between 3.91–500 µg/mL, with most compounds having moderate to good activities (MIC N-benzyl group. In addition to antimycobacterial activity assessment, final compounds were screened for their in vitro cytotoxicity. N-(naphthalen-1-ylmethyl)quinoxaline-2-carboxamide (compound 29) was identified as a potential antineoplastic agent with selective cytotoxicity against hepatic (HepG2), ovarian (SK-OV-3), and prostate (PC-3) cancer cells lines. Molecular docking showed that human DNA topoisomerase and vascular endothelial growth factor receptor could be potential targets for 29.

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