Evaluation 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.

Our previous work have identified a novel oxazolidinones structure, biaryloxazolidinone analogues containing a hydrazone moiety, as promising antibacterial agents against Gram positive strains. Based on these active structure, we synthesized a series novel oxazolidinones here and determine their anti-Mycobacterial activities in vitro and in Mycobacterium marinum (M.marinum) infected Zebra fish. The in vitro anti-Mycobacterial assay demonstrated that all of them have potent efficacy against both H37Rv and clinical Mycobacterial isolates. Among of these active agents, (S)-N-(3-(2-fluoro-4'-(2-amino-4-thiazolyl)biphenyl-4-yl)-2-oxo-1,3-oxazolidie-5-yl methyl)acetamide (compound 7), whose in vitro MIC was 10 fold lower than linezolid, showed the strongest bactericidal effects, with ~2.2 log reduction of M.marinum load in Zebra fish at 10mg/kg. Other novel oxazolidinones, compound 9, 12, 16, and 21 showed reduction range against M.marinum at 1.1-1.8 log, which showed better efficacy than linezolid did. Our results indicate that these identified compounds could be further developed as novel anti-Mycobacterial agents.