The reaction of imidazole-5-carbohydrazide
1 with hydrazonyl halides
2a,
b gave the corresponding hydrazide–hydrazone derivatives
3a,
b. Afterwards, 3-methyl-5-(4-methyl-2-aryl-1
H-imidazol-5-yl)-4-(2-phenylhydrazineylidene)-4
H-pyrazole
4a,
b was affordably produced by cyclizing the latter compounds
3a,
b in EtOH with
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The reaction of imidazole-5-carbohydrazide
1 with hydrazonyl halides
2a,
b gave the corresponding hydrazide–hydrazone derivatives
3a,
b. Afterwards, 3-methyl-5-(4-methyl-2-aryl-1
H-imidazol-5-yl)-4-(2-phenylhydrazineylidene)-4
H-pyrazole
4a,
b was affordably produced by cyclizing the latter compounds
3a,
b in EtOH with Et
3N at reflux temperature. The corresponding piperidinyl, morpholinyl, and piperazinyl derivatives
5a–f were produced by a nucleophilic substitution reaction of
3a,
b with piperidine, morpholine, and 1-methylpiperazine in EtOH at reflux temperature. The condensation reaction of carbohydrazide
1 with either 3-acetyl-2
H-chromen-2-one or 1-(benzofuran-2-yl)ethan-1-one in EtOH with AcOH at reflux temperature yielded the corresponding hydrazones
6 and
7, respectively, in excellent yields. Twelve compounds were evaluated for their antibacterial properties and to ascertain their minimum inhibitory concentrations utilizing well diffusion methods. All compounds showed differing levels of antibacterial efficacy depending on the microbial species. Compounds
4b and
5c had the most favorable results, with inhibition zones of 2.7 cm against the Gram-positive bacterium
S. aureus, with a minimum inhibitory concentration (MIC) of 50 µg/mL. Compounds
4b and
5c, demonstrating the highest activity, were subjected to molecular docking investigations to evaluate their inhibitory effects on the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase [GlcN-6-P] of 2VF5. The molecular docking results revealed that both
4b and
5c exhibited a minimum binding energy of −8.7 kcal/mol, whereas the natural ligand GLP displayed a binding energy of −6.2 kcal/mol, indicating a substantial affinity for the active site; thus, they may be considered potent inhibitors of GlcN-6-P synthase.
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