Exploring Biofilm Inhibition Potential of Imidazo-Pyridine Linked Tetrazoles Against Candida albicans: Synthesis, Biological Evaluation With Computational Studies.

Infectious diseases remain one of the major global health challenges due to their rapid transmission and evolving pathogenic mechanisms. Among them, Candida albicans has emerged as a significant opportunistic antifungal pathogen, which is responsible for biofilm-associated infections. In the present study, a library of new tetrazole bearing imidazo-pyridine molecules (4a-4j) was synthesised and characterised through spectroscopic techniques (1H, 13C and MS) for structural confirmation. Their in vitro antifungal potential was evaluated against C. albicans, where compound 4d emerged as the most promising lead among all by exhibiting a MIC of 7 μg/mL and MFC of 45 μg/mL, conquering the reference fluconazole (FLC) which showed 8 μg/mL and 64 μg/mL of MIC and MFC, respectively. Compound 4d also demonstrated 75% and 86% inhibition of fungal filamentation and of biofilm formation, respectively. qRT-PCR analysis confirmed the significant downregulation of important virulence genes, and SEM imaging further validated biofilm prevention. Toxicity assessment through hemolytic and cytotoxic assays on HEK293 cell line indicated low toxicity across tested concentrations. Additionally, computational evaluation including molecular docking and ADMET parameters supported the predicted binding affinities and pharmacokinetic properties of the synthesised compounds.