Synthesis and antifungal assessment of imidazole-containing compounds: A comprehensive study integrating experimental and computational techniques

The emergence of resistant fungal strains has created an urgent need for novel antifungal agents with improved efficacy and safety profiles. In this study, we report the design, synthesis, and evaluation of a new series of imidazole-containing thiazole derivatives as potential anti-fungal agents. The compounds were synthesized via a two-step process involving thiourea formation, followed by microwave-assisted cyclization with substituted phenacyl bromides. The resulting products, mostly semi-liquid in nature, were characterized by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy.The synthesized derivatives were tested in vitro against clinically relevant fungal pathogens, including Candida albicans, Candida glabrata, Candida parapsilosis, and Candida krusei. Structure-activity relationship (SAR) analysis indicated that the antifungal activity was influenced by the electronic and steric properties of the aromatic substituents. Compound 2b, bearing a para-cyano group, exhibited the highest potency, with MIC50 values of 0.98 µg/mL against C. albicans and C. parapsilosis, comparable to standard antifungal agents. Molecular docking studies supported these findings, revealing favorable interactions with fungal target sites, and ADME predictions suggested drug-like properties. This multidisciplinary approach led to the identification of imidazole-based compounds with potent anti-fungal properties, laying the groundwork for further optimization and preclinical development.