Exploration of Benzofuran/Indole‐Chalcone Conjugated 1,2,3‐Triazole Hybrids as <i>Candida glabrata</i> Agents: Design, Synthesis, Biological Evaluation, Molecular Docking, and In Silico ADMET Analysis

A novel series of benzofuran/indole-chalcone linked 1,2,3-triazole hybrids (4a-k, 8a-h) were synthesized to explore their potential as antifungal agents. Among the 19 derivatives, 4b, 4c, 4i, 4j, and 8a showed inhibition against Candida glabrata at 50 µg/mL concentration that is comparable to the control drug fluconazole. Compounds 4b, 4c, and 4j showed greater activity at low concentrations (25 and 12.5 µg/mL). Among them, 4j exhibited the highest potency, with 81.82% inhibition against C. glabrata at 50 µg/mL. Compound 4j exhibited better safety profiles against human acute monocytic leukemia cells. In structural activity studies, chloro (Cl) at the 2,6th position of the phenyl ring of chalcone and p-CN substitution on the benzyl triazole moiety maximizes the potential. In addition, in silico ADME analysis supports the drug-likeness profile and strengthens the data. So, compound 4j can be used as an effective lead to develop a potent and safer antifungal drug candidate to combat Candida infections.