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.

Abstract

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.