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

doi:10.6023/cjoc202001017

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (9): 2817-2826.DOI: 10.6023/cjoc202001017 Previous Articles Next Articles

新型3-芳乙烯基喹喔啉-2-羧酸合成及结核杆菌亮氨酰-tRNA合成酶的抑制活性研究

李阳^a, 董时雨^a, 秦洪伟^a, 唐冰月^a, 高文涛^a, 陈羽^b

a 渤海大学化学化工学院辽宁锦州 121000;
b 沈阳药科大学生命科学与生物制药学院沈阳 110016

收稿日期:2020-01-11 修回日期:2020-05-28 发布日期:2020-07-01
通讯作者: 高文涛, 陈羽 E-mail:bhuzh@163.com;isfc_bhu@yeah.net
基金资助:
国家自然科学基金（Nos.21878023，U1608222，41602351）、辽宁省博士启动基金（No.2019-BS-004）和辽宁省教育厅科学基金（No.LQ2019006）资助项目.

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

Li Yang^a, Dong Shiyu^a, Qin Hongwei^a, Tang Bingyue^a, Gao Wentao^a, Chen Yu^b

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:2020-01-11 Revised:2020-05-28 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).

1. cjoc202001017辅助材料.pdf(2374KB)

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.

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新型3-芳乙烯基喹喔啉-2-羧酸合成及结核杆菌亮氨酰-tRNA合成酶的抑制活性研究

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

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