Fungicidal effects of some derivatives of 2-ferrocenyl-benzimidazoles: A possible template for antifungal drug design

The minimum inhibitory concentration (MIC) and minimum, fungicidal concentration (MFC) for a group of newly synthesized derivatives of 2-ferrocenyl-5-fluoro-6-(4-substituted-1-pipera-zinyl) benzimidazoles were determined using a broth macrodilution method following clinical and laboratory standards institute (CLSI) recommendation for medically important Candida sp. The data demonstrate that compounds 4-fluoro-5-(4-methyl-1-piperazinyl)-2-nitroaniline(5a), 4-Fluoro-5-(4-phenyl-1-piperazinyl)-2-nitroaniline(5b), 2-ferrocenyl-5-fluoro-6-(4-methyl-1-piperazinyl) benzimidazole (7a), 2-ferrocenyl-5-fluoro-6-(4-phenyl-1-piperazinyl) benzimidazole (7b) and 2-ferrocenyl-5-fluoro-6-[4-(4-fluorophenyl)-1-piperazinyl] benzimidazole (7e) were found to have potent in vitro antiftingal activity with MICs at which 80% of the strains were inhibited (MIC₈₀s) of 15-125 μg mL^-1. The active compounds were further screened in order to establish their mode of action on the basis of inhibitory effects on growth, budding, germ-tube formation and leakage of cytoplasmic content release after treatment. In comparison to control drugs (e.g., nystatin, miconazole nitrate, and ketoconazole). Some derivatives of the 4-fluoro-5-(4-substituted-1-piperazinyl)-2-nitroanilines (series 5) and 2-ferrocenyl-5-fluoro-6-(4-substituted-1-piperazinyl)-[1H] benzi-midazoles (series 7) were found to be more potent in lower micro-molar concentrations (15-500 μg mL^-1). It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and in vivo efficacies of these compounds are warranted to determine their clinical potential.