Synthesis and antifungal activities of some benzimidazolyl-chalcones, analogues of chlormidazole

We report here the synthesis of new benzimidazolyl-chalcones analogues of chlormidazole in order to contribute to the development of new antifungal drugs. Benzimidazolyl-chalcones were obtained by reaction of various aromatic aldehydes (7) with N-(4-chlorobenzyl)-2-acetylbenzimidazole (5) and its precursor 2-acetylbenzimidazole (4). After confirming their structure using spectroscopic methods ( 1 H and 13 C NMR, MS in EI mode), the compounds were evaluated for their antifungal activities against a clinical strain of Candida albicans in order to determine the minimum inhibiting quantity (MIQ). This screening showed that compounds 6e, 6f and 6h had anti-Candida efficiencies (MIQ = 5, 1.25 and 0.625 μg) higher than those of chlormidazole (MIQ = 10 μg). Additionally it has shown that improving these activities in benzimidazolyl-chalcones series requires double chemical modulation: Removal of 4chlorobenzyl on the pyrrole nitrogen of the benzimidazole ring and the introduction or not of modulators such as fluorine (compounds 6f and 6h) on the benzene ring at position 3 of the propenone.