An efficient synthesis, characterization, and in silico studies of novel chromenes, thiophenes, pyrazolo[1,5-a]pyrimidines, and pyrimidines as potential antimicrobial and anticancer agents using the bio-buffer tris(hydroxymethyl)aminomethane (THAM)

Abstract

Novel 2-imino-6-(aryldiazenyl)-2H-chromene-3-carboxamides 6a–e, 2-amino-4H-cyclopenta or benzo[b]thiophene-3-carboxamides 10a,b, 2,7-diaminopyrazolo[1,5-a]pyrimidine-6-carboxamides 13a–e, pyrimidine-5-carboxamides 14, 15 and 3-amino-1H-pyrazole-4-carboxamide 16 were synthesized from the reaction of 2-cyano-N-(1,3-dihydroxy-2-(hydroxyl-methyl) propan-2-yl) acetamide 2 with 4-arylazosalicylaldehydes 5a-e, cyclopentanone and/or cyclohexanone, guanidine derivatives and hydrazine hydrate, respectively. Some new compounds were evaluated for antibacterial activity in vitro, and exhibited good efficacy compared to gentamicin. Compound 4c showed greater activity against gram negative bacteria (Klebsiella pneumonia and Pseudomonas aeruginosa) than standard antibiotic. Compound 4c with two withdrawing groups also showed the higher activity (38.7 ± 0.6) against fungi (Candida albicans) than the Nystatin (20 ± 0.5). On the other hand, compounds 13a, 13c, and 13e have strong cytotoxic activity among the tested compounds in the three selected cancer cell lines (HePG2, MCF7 and Hela). Physicochemical characterization by Swiss ADME predication was also performed for some synthesized compounds exhibiting better biological and antimicrobial properties.