Synthesis and Biological Assessment of New Thiazoles for Mycobacterial Infections and Biofilm Disruption

Sixteen thiazoles, of which nine are unprecedented substances (11, 12, 15, 16, 17, 19, 20, 23, and 24), were obtained by a cyclocondensation reaction between a thioamide and an α-bromoketone, via Hantzsch synthesis. All thiazoles (11-26), along with four thiosemicarbazone derivatives (7-10) and their precursors (1-6), were evaluated for their activity against Mycobacterium species Mycobacterium abscessus, Mycobacterium massiliense, Mycobacterium fortuitum, and Mycobacterium smegmatis, as well as for their antibiofilm properties. Among them, compounds 7, 8, 14, 17, 18, 19, 20, and 21 showed promising results in minimum inhibitory concentration (MIC) assays, demonstrating bactericidal activity within 48 h. Moreover, all these compounds inhibited biofilm formation. Notably, the unprecedented thiazole 17, along with 18 (MIC = 36 μmol L^-1) and 21 (MIC = 65 μmol L^-1), exhibited the lowest MIC values against all tested species, outperforming the reference drugs. Furthermore, these compounds showed a high degree of selectivity toward mycobacterial cells, as confirmed by cytotoxicity assays using peripheral blood mononuclear cells (PBMC) and Vero cells. These findings highlight the strong antimycobacterial potential of the new thiazole derivatives, warranting further investigation.