Synthesis and in vitro Evaluation of the Antimycobacterial Activity of N-aryl-1,4-dihydropyridine-3,5-dicarboxamides

Dihydropyridines (DHPs) with carboxamides in the 3 and 5 positions show anti-tuberculosis activity. The purpose of the present study was to synthesize new DHPs that would possibly possess anti-tuberculosis activity. So a series of N-aryl-1,4-dihydropyridine-3,5-dicarboxamides (3-38) was prepared. They were screened as antitubercular agents against one type of fast growing Mycobacterium (M. smegmatis). The compounds that passed this first screening were then tested against slow-growing Mycobacterium (BCG). Minimum bacteriocidal concentrations (MBCs) were determined using the agar proportion method. The cytotoxic effect of two active compounds against HeLa cell lines was determined using an MTT assay method. N,N-Bisphenyl-4-[1-(4-fluorobenzyl)-2-methylthioimidazole-5-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxamide 27 and N,N-bisphenyl-4-[1-(2-chlorobenzyl)-2-methylthioimidazole-5-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxamide 33 were the most potent compounds tested, showing MBCs of 16 and 32 µg/ml, respectively. Their activities were comparable to that of isoniazid (32 µg/ml). In the MTT assay, these two compounds showed moderate toxicity.