Design, synthesis and biological activity of pyrazinamide derivatives for anti-Mycobacterium tuberculosis

Abstract

A total of 11 pyrazinamide derivatives were designed and synthesised using pyrazinamide as the lead compound, which was optimised by structural modification with alkyl chains, six-membered rings, and bioisosterism, respectively. The target compounds were synthesised using pyrazinecarboxylic acid as the starting material by acylation, amidation, and alkylation, respectively. Their structures were confirmed by ¹H NMR, ¹³C NMR, HRESIMS, and elemental analysis, respectively. The bioactivities of derivatives were assayed using bacteriostatic experiment and minimum inhibitory concentration experiment. It was showed that the derivatives had good inhibitory effect on Mycobacterium tuberculosis. The biological activity of derivative 1f was the best among all compounds, its antibacterial activity was 99.6%, and the minimum inhibitory concentration was 8.0 µg/mL.

Keywords:

• Pyrazinamide
• derivatives
• design
• synthesis
• biological activity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The project was sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry. The work was also supported by Chongqing Scientific & Technological Innovation Special Project of Social Undertakings and People's Livelihood Guarantee [No. cstc2015shmszx80060], Chongqing Key Research Project of Basic Science & Frontier Technology [No. cstc2017jcyjBX0012], Scientific and Technological Research Program of Chongqing Municipal Education Commission [Grant No. KJ1400523], Foundation Project of Chongqing Normal University [No. 14XYY020], Chongqing General Research Project of Basic Science & Frontier Technology [No. cstc2015jcyjA10054], Chongqing Normal University Postgraduate’s Research and Innovation Project [No. YKC17004], Open Foundation Project of University Engineering Research Center for Bioactive Substances in Chongqing [No. AS201614], Chongqing University Students’ Training Project of Innovation & Undertaking [No. 201610637076], China.