Oxadiazole and hydrazone derivatives of benzimidazothiazine as potential antifungal and anti-tubercular agents.

The current study focuses on the synthesis and pharmacological evaluation of novel oxadiazole and hydrazone derivatives of 4-oxo-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazine-2-carbohydrazides (5a-f and 6a-f). The compounds were synthesised via a conventional reflux method and characterized using FT-IR, NMR (1H and 13C), and LC-MS techniques. Antifungal activity of all compounds was evaluated against Candida albicans using the broth microdilution method, and compounds 6b and 6 f showed greater inhibitory potential than the reference drug, Fluconazole. Biofilm inhibition assay, supported by SEM analysis, showed notable inhibitory effects, particularly for compounds 6b and 6 f, and strong suppression of hyphal development, as analyzed in the filament inhibition assay. In addition, biofilm gene expression was assessed by RT-PCR for the target compounds, demonstrating greater inhibitory effects on gene expression for 6b and 6 f than for Fluconazole. Furthermore, in silico studies identified compounds 6b and 6 f as potential lead candidates due to their multi-target interactions with Candida albicans virulence-associated proteins. The anti-tubercular activity was evaluated on Mycobacterium tuberculosis (H37Rv strain, ATCC No. 27294), in which the compound 5a from the oxadiazole series exhibited good anti-tubercular activity, and in the hydrazone series, the compound 6b exhibited excellent anti-tubercular activity.