Synthesis, antioxidant, and antimicrobial activities of new 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitriles, (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl)methanones, and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5-]pyridine-8-carbonitriles

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Abstract

Objectives
A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitrile (, ), (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl) methanone (–), and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5-]pyridine-8-carbonitrile (–) derivatives were synthesized and evaluated for their antioxidant and antimicrobial activities; in addition, their quantitative structure–activity relationships and molecular docking were investigated.
Methods
The target compounds , were synthesized by the following method: reaction of 5,6-dimethyl-1H-benzoimidazole-2-carbohydrazide () with 4-(dimethyl amino)benzaldehyde or anthracene-9-carbaldehyde yielded Schiff’s bases ,, which were reacted with ethyl cyanoacetate to yield 1H-pyrazole-4-carbonitriles ,; -methylation of , afforded ,, which reacted with 4-aminoantipyrine to give ,. In addition, 5-benzoyl-1H-benzo[d]imidazole-2-carbohydrazide () or 8-cyano-6-isocyano-5-oxo-7-phenyl-1,5-dihydro-[1,2,4]triazolo[1,5-]pyridine-2-carbohydrazide () reacted with different carboxylic acids such as crotonic acid, 3,4-diaminobenzoic acid, and 6-hydroxy-4-methoxybenzofuran-5-carboxylic acid to form compounds – and –, respectively. The synthesized compounds were evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, and the diffusion plate method for antimicrobial activity.
Results and conclusion
Among other tested compounds, compounds , , and possessed the highest antioxidant activity, whereas compounds , , , , and displayed high activity against , , and . The quantitative structure–activity relationships of the studied compounds , , , , , , , , and indicated a high correlation (=0.82) between the predicted and actual activities as obtained from molecular descriptors and the inhibitory activity of this set of tested molecules measured as antioxidant activity. Moreover, the three-dimensional (3D) pharmacophore was generated, and docking of the most active antibacterial compound against the dihydropteroate synthase enzyme gave comparable scores for hydrogen bond interaction (−13.5 kcal/mol) and binding mode to the reference antibiotic sulfamethoxazole (−13.00 kcal/mol).

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Egyptian Pharmaceutical Journal
Volume 11, Issue 2
December 2012
Pages 80-92

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