Exploration of Novel TOSMIC Tethered Imidazo[1,2-a]pyridine Compounds for the Development of Potential Antifungal Drug Candidate.

New candidates of imidazo[1,2-a]pyridine were designed by combining 2-amino pyridine, TOSMIC and various assorted aldehydes to explore their antioxidant and antifungal potential. The design of these derivatives was based on utilizing the antifungal potential of azoles and TOSMIC moiety. These derivatives were synthesized by adopting multi-component reaction methodology, as it serves as a rapid and efficient tool to target structurally diverse heterocyclic compounds in quantitative yield. The resulting imidazo[1,2-a]pyridine derivatives were structurally verified by 1 HNMR, 13 CNMR, HRMS, and HPLC. The compounds were analyzed for their antioxidant and fluorescent properties and it was observed that compound 15 depicted highest potential. The compounds were evaluated for their antifungal potential to highlight their medical application in the area of Invasive Fungal Infections (IFI). Compound 12 gave the highest antifungal inhibition against Aspergillus fumigatus 3007 and Candida albicans 3018. To elucidate the antifungal mechanism, confocal images of treated fungi were analyzed, which depicted porous nature of fungal membrane. Estimation of fungal membrane sterols by UPLC indicated decrease in ergosterol component of fungal membrane. In silico studies further corroborated with the in vitro results as docking studies depicted interaction of synthesized heterocyclic compounds with amino acids present in the active site of target enzyme (lanosterol 14 alpha demethylase). Absorption, distribution, metabolism, and excretion (ADME) analysis was indicative of drug-likeliness of the synthesized compounds.