Synthesis and Anticandidal Activity of New 6-Chloroimidazo[1,2-a]pyridine Derivatives

Aims: The general objective assigned to this work was to contribute to the pharmacochemical development of new antifungal drugs derived from 6-Chloroimidazo [1,2-a]pyridine.This preliminary study was conducted on Candida parapsilosis, which is an increasingly difficult organism to treat. Methodology: The imidazo [1,2-a] pyridinylacrylonitriles designed by juxtaposition of bioactive entities were synthesized in three steps. Firstly, this involves the synthesis of the imidazopyridine core via cyclocondensation. Then,its functionalization at position 2 with an acetonitrile group, and finally condensation of the resulting intermediate with various aromatic aldehydes Results: A total of ten derivatives of (6-chloroimidazo [1,2-a]pyridin-2-yl)-phenylacrylonitrile were obtained, with yields ranging from 63% to 92%. The biological evaluation focused on the antifungal activity of these compounds against a clinical strain of Candida parapsilosis, with minimum inhibitory concentrations (MIC) ranging from 19.36 µM to 89.38 µM. Structure–activity relationship (SAR) analysis revealed that the nature and position of the substituent on the aryl ring significantly modulate antifungal efficacy. These findings highlight the pharmacochemical relevance of electron-withdrawing or polarizable substituents in enhancing antifungal activity. Conclusion: Due to their innovative profile combining a functional chain and a bioactive pharmacophore, these novel imidazo[1,2-a]pyridine hybrids appear as promising candidates for the development of potent antifungal agents, particularly against Candida species.