Synthesis, antifungal and antimycobacterial activities of new bis-imidazole derivatives, and prediction of their binding to P45014DM by molecular docking and MM/PBSA method ☆

Abstract New bis-imidazole derivatives have been synthesized and their antifungal and antimycobacterial activity was determined. Almost all compounds exhibited a moderate to good activity against two clinical isolates of Candida albicans 3038 and Candida glabrata 123. The same compounds showed an interesting killing activity against Mycobacterium tuberculosis H 37 Rv reference strain. Docking procedures combined with molecular dynamics simulations in the MM/PBSA framework of theory were applied to predict the binding mode of all compounds in the binding pocket of the cytochrome P450 14α-sterol demethylase (14DM) of C. albicans , for which no ligand–protein crystal structure is currently available. The results obtained in silico showed that the active compounds may interact at the active site of protein, and that their binding free energy values are in agreement with the corresponding experimental activity values.