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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 9: 2817 - 2826

DOI: https://doi.org/10.6023/cjoc202001017

A Facile Synthesis and M. tuberculosis Leucyl-tRNA Synthetase Inhi-bitory Activity of Novel 3-Arylvinylquinoxaline-2-carboxylic Acids

  • Li Yang ,
  • Dong Shiyu ,
  • Qin Hongwei ,
  • Tang Bingyue ,
  • Gao Wentao ,
  • Chen Yu
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  • a College of Chemistry and Chemical Engineering, Bohai University, Jinzhou, Liaoning 121000;
    b School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016

Received date: 2020-01-11

  Revised date: 2020-05-28

  Online published: 2020-07-01

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 21878023, U1608222, 41602351), the Doctoral Start-up Foundation of Liaoning Province (No. 2019-BS-004) and the Scientific Research Foundation of the Education Department of Liaoning Province (No. LQ2019006).

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Abstract

In the present work, a simple and facile synthesis of a new series of 3-arylvinylquinoxaline-2-carboxylic acids has been achieved using the newly-synthesized ethyl 3-bromomethylquinoxaline-2-carboxylate as substrate through one-pot sequential Arbuzov/Horner-Wadsworth-Emmons (HWE)/ester hydrolysis reaction procedure. A primary in vitro evaluation for their inhibitory activity against Mycobacterium smegmatis (M. smegmatis) Leucyl-tRNA synthetase (Mtb LeuRS) revealed that (E)-3-(3-nitrostyryl)quinoxaline-2-carboxylic acid (5j) represented the most active compound in this round of effort with the IC50 value of 14.7 μmol·L-1, which was much superior to the reference drug AN2679, indicating the potential medicinal value for the exploration of novel Mtb LeuRS inhibitor. The results of molecular docking analyses using CDOCKER module of Discovery Studio (DS) software suggested that it could bind well to the active site of Mtb LeuRS. Moreover, the antitubercular assay against M. smegmatis also revealed that the nitro-substituted 5j has the best anti-tubercular activity with the minimum inhibitory concentration (MIC) value 15.6 μg/mL, being comparable with the reference rifampicin.

Key words： quinoxaline; bromination reaction; one-pot three-step; M. smegmatis; Leucyl-tRNA synthetase

Cite this article

Li Yang , Dong Shiyu , Qin Hongwei , Tang Bingyue , Gao Wentao , Chen Yu . A Facile Synthesis and M. tuberculosis Leucyl-tRNA Synthetase Inhi-bitory Activity of Novel 3-Arylvinylquinoxaline-2-carboxylic Acids[J]. Chinese Journal of Organic Chemistry, 2020 , 40(9) : 2817 -2826 . DOI: 10.6023/cjoc202001017

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