Evaluation of the Anti-Mycobacterial Activity of Newly Synthesized (S)-N-(3-(2-Fluoro-4'-(2-Amino-4-Thiazolyl)Biphenyl-4-Yl)-2-Oxo-1,3-Oxazolidie-5-Ylmethyl) Acetamide Derivative in Vitro and in Mycobacterium marinum-Infected Zebrafish

• Published in: Japanese Journal of Infectious Diseases Vol. 74; no. 3; pp. 245 - 248
• Main Authors: Ding, Xiudong, Wu, Yachuang, Tong, Aihua, Sun, Bin, Zhao, Yanfang, Jiang, Ying
• Format: Journal Article
• Language: English
• Published: National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 31.05.2021
• Subjects: anti-mycobacterial activities; linezolid; MmIZ model; oxazolidinones
• ISSN: 1344-6304; 1884-2836
• DOI: 10.7883/yoken.JJID.2020.307

Through our previous work, we have identified that novel oxazolidinone structures, the biaryloxazolidinone analogues containing a hydrazone moiety, act as promising antibacterial agents against gram-positive bacterial strains. Based on this active structure, in this study, we synthesized a series of novel oxazolidinones and determined their anti-mycobacterial activities in vitro and in Mycobacterium marinum-infected zebrafish. The in vitro anti-mycobacterial assay demonstrated that all of the synthesized compounds have potent efficacy against both H37Rv and clinical mycobacterial isolates. Among all the generated active agents, (S)-N-(3-(2-fluoro-4'-(2-amino-4-thiazolyl)biphenyl-4-yl)-2-oxo-1,3-oxazolidie-5-ylmethyl)acetamide (compound 7), whose in vitro MIC was 10-fold lower than that of linezolid, showed the strongest bactericidal effects, with ~2.2-log reduction of M. marinum load in zebrafish at 10 mg/kg dosage. Other novel oxazolidinones, compounds 9, 12, 16, and 21, exhibited reduction range of 1.1–1.8 log against M. marinum and displayed better efficacy than linezolid. Our results indicate that these identified compounds have the potential to be further developed as novel anti-mycobacterial agents.