Design and Evaluation of Antimicrobial Activity of New Pyrazole, 1,2,4-Triazole, and 1,3,4-Thiadiazol Derivatives Bearing 1,4-Dihydroquinoxaline Moiety

Abstract

An effective method for synthesizing a series of fifteen new compounds ethyl 3-(2-(3-amino-1,4-dihydroquinoxaline-2-carbonyl)hydrazono )butanoate (II), 3-amino-N'-benzylidene-1,4-dihydroquinoxaline-2-carbohydrazide derivatives (IV–VI), phenyl)-4-oxothiazolidin-3-yl)-1,4-dihydroquinoxaline-2-carboxamide derivatives (VII–IX), 3-(3-amino-1,4-dihydroquinoxalin-2-yl)-5H-[1,2,4]triazolo[3,4-a]isoindol-5-one (X), 1,4-dihydroquinoxaline-2-carbonyl)-N-substituted hydrazine carbothioamide (XI–XII), 5‑(3-amino-1,4-dihydroquinoxalin-2-yl)-4-substituted-4H-1,2,4-triazole-3-thiol (XIII–XIV) and 5-(3-amino-1,4-dihydroquinoxalin-2-yl)-N-substituted-1,3,4-thiadiazol-2-amine (XV–XVI) based on 1,4-dihydroquinoxaline moiety in 60–85% yields starting from reaction of hydrazide 3-Amino-1,4-dihydroquinoxaline-2‑carbohydrazide (I) with ethyl acetoacetate has been proposed. The designed compounds have been successfully screened in vitro for their antibacterial and antifungal activities. Structural identifications of the obtained products have been carried out by spectroscopic techniques including FTIR, 1H NMR, 13C NMR, and mass spectroscopy. The relation between the structure of the synthesized compounds and their activity against selected bacteria and fungi was studied and favorable results were obtained. The majority of tested compounds showed moderate antibacterial activities except compound 3-amino-N-(2-(4-chlorophenyl)-4-oxothiazolidin-3-yl)-1,4-dihydroquinoxaline-2-carboxamide (VIII) that notably exhibited the most potent antibacterial activity against the tested Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacteria. Further antifungal studies indicated that the compounds Ethyl 3-(2-(3-amino-1,4-dihydroquinoxaline-2-carbonyl)hydrazono) butanoate (II), 3-amino-N-(2-(4-chlorophenyl)-4-oxothiazolidin-3-yl)-1,4-dihydroquinoxaline-2-carboxamide (VIII), 3-amino-N-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)-1,4-dihydro quinoxaline-2-carboxamide (IX) and 2-(3-amino-1,4-dihydroquinoxaline-2-carbonyl)-N-phenyl hydrazine carbothioamide (XI) exerted the highest antifungal activities against Aspergillus flavus and Candida albicans fungi.