Synthesis and Antifungal Activity of 6-Chloroimidazo[1,2-a]pyridinyl-Chalcones Against Aspergillus Flavus

Abstract

Aims: This pharmacochemical study aimed to design, synthesize, structurally characterize, and evaluate the anti-aspergillus activity of a new series of 6-chloroimidazo[1,2-a]pyridinyl–chalcone derivatives against an environmental strain of Aspergillus flavus, a major opportunistic fungal pathogen of high priority in the context of invasive fungal infections. Methodology: The target compounds were synthesized via Claisen–Schmidt condensation between 3-acetyl-6-chloro-2-methylimidazo[1,2-a]pyridine and a range of substituted aromatic aldehydes under basic conditions. The structures of the synthesized derivatives were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, which validated the formation of the expected α,β-unsaturated carbonyl systems characteristic of chalcones. The antifungal activity of the compounds was assessed in vitro using a microdilution method in microplates, and minimum inhibitory concentrations (MICs) were determined to quantify their antifungal effects. Results: A total of ten 6-chloroimidazo[1,2-a]pyridinyl–chalcone hybrids were successfully obtained with yields ranging from 32% to 68%. The antifungal evaluation revealed MIC values between 75.48 and 160.89 µM. Notably, the 2-chloro-, 2-methoxy-, and 3-methoxy-substituted derivatives displayed the most potent activity, with MIC values around 75–76 µM. Conclusion: These results highlight the promising antifungal potential of 6-chloroimidazo[1,2-a]pyridinyl–chalcone hybrids and suggest that they represent valuable lead structures for the further development of novel antifungal agents targeting Aspergillus flavus.