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

摘要

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 (1H and 13C 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 4-chlorobenzyl 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.