Newly synthesized imidazolotriazole, imidazolotriazine, and imidazole-pyrazole hybrid derivatives as promising antimicrobial agents

Abstract

Novel 1-(3-(4-bromophenyl)-5-methyl-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethan-1-one 1 was synthesized through a one-step reaction and allowed to react with ethyl bromoacetate followed by hydrazine hydrate to produce 1-(1-(4-bromophenyl)-2-hydrazinyl-4-methyl-1H-imidazol-5-yl)ethan-1-one (4), which was subjected to various cyclization reactions in the presence of carbon disulfide, benzoyl chloride, acetic anhydride, triethyl orthoformate, phenyl isothiocyanate, and potassium thiocyanate to obtain imidazolotriazoles 6–11. Moreover, imidazole-pyrazole hybrids 12–14 were obtained upon treatment of 2-hydrazino-imidazole derivative 4 with different active methylene compounds, namely, diethyl malonate, ethyl cyanoacetate, and acetylacetone. Finally, imidazolotriazines 15–17 and imidazole-pyrrole hybrid 18 and 19 were prepared by heating derivative 4 in the presence of diethyl oxalate, bromoacetic acid, 1,2-dichloroethane, maleic anhydride, and phthalic anhydride. All newly prepared derivatives containing an imidazole nucleus were evaluated against Escherichia coli (Gram-negative bacteria, NCTC-10416), Staphylococcus aureus (Gram-positive bacteria, NCTC-7447), and Candida albicans (fungi; NCCLS 11). Compounds 16, 6, 12 and 18 presented excellent antimicrobial potency against Gram-positive bacteria which were 1.64%, 3.28%, 9.84%, and 16.39% higher than that of the common reference drug streptomycin, respectively. Furthermore, compounds 6, 12, 15, 16, and 18 showed excellent antimicrobial activities against Gram-negative bacteria, outperforming streptomycin by 38.77%, 30.61%, 67.35%, 48.98%, and 24.49%, respectively. Finally, compound 13 exhibited an excellent antifungal performance, which was 6.94% higher than that of the common reference drug griseofulvin.