Egyptian Pharmaceutical Journal

ORIGINAL ARTICLE
Year
: 2012  |  Volume : 11  |  Issue : 2  |  Page : 80--92

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-a]pyridine-8-carbonitriles ( QSAR and molecular docking analysis)


Fatma A. Bassyouni1, Hanaa A. Tawfik2, Ahmed R. Hamed3, Maha M. Soltan3, Mahmoud ElHefnawi4, Ahmed A. ElRashedy4, Maysa E. Moharam5, Mohamed Abdel Rehim6 
1 Department of Chemistry of Natural and Microbial Products; Pharmaceutical Research Group, Center of Excellence for Advanced Sciences, Cairo, Egypt
2 Department of Chemistry of Natural and Microbial Products, Centre of Excellence for Advanced Sciences, Cairo, Egypt
3 Pharmaceutical Research Group; Department of Chemistry of Medicinal Plants, Centre of Excellence for Advanced Sciences, Cairo, Egypt
4 Biomedical Informatics and Chemo Informatics Group, Department of Informatics and Systems, Centre of Excellence for Advanced Sciences, Cairo, Egypt
5 Department of Microbial Chemistry, National Research Centre, Dokki, Cairo, Egypt
6 Department of Analytical Chemistry, Stockholm University, Stockholm, Sweden

Correspondence Address:
Fatma A. Bassyouni
PhD, Department Chemistry of Natural and Microbial Products and Pharmaceutical Research Group, Center of Excellence for Advanced Sciences, National Research Centre, 12311 Cairo
Egypt

Objectives

A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitrile (6a,b), (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl) methanone (911), and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile (1416) 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 6a,b were synthesized by the following method: reaction of 5,6-dimethyl-1H-benzoimidazole-2-carbohydrazide (2) with 4-(dimethyl amino)benzaldehyde or anthracene-9-carbaldehyde yielded Schiff’s bases 3a,b, which were reacted with ethyl cyanoacetate to yield 1H-pyrazole-4-carbonitriles 4a,b; N-methylation of 4a,b afforded 5a,b, which reacted with 4-aminoantipyrine to give 6a,b. In addition, 5-benzoyl-1H-benzo[d]imidazole-2-carbohydrazide (8) or 8-cyano-6-isocyano-5-oxo-7-phenyl-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-2-carbohydrazide (13) reacted with different carboxylic acids such as crotonic acid, 3,4-diaminobenzoic acid, and 6-hydroxy-4-methoxybenzofuran-5-carboxylic acid to form compounds 911 and 1416, 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 15, 11, and 10 possessed the highest antioxidant activity, whereas compounds 4a, 5b, 6b, 10, and 11 displayed high activity against Staphylococcus aureus, Salmonella typhimurium, and Candida albicans. The quantitative structure–activity relationships of the studied compounds 4a, 4b, 5b, 6b, 10, 11, 14, 15, and 16 indicated a high correlation (r 2=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 4a 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).




How to cite this article:
Bassyouni FA, Tawfik HA, Hamed AR, Soltan MM, ElHefnawi M, ElRashedy AA, Moharam ME, Rehim MA. 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-a]pyridine-8-carbonitriles ( QSAR and molecular docking analysis).Egypt Pharmaceut J 2012;11:80-92


How to cite this URL:
Bassyouni FA, Tawfik HA, Hamed AR, Soltan MM, ElHefnawi M, ElRashedy AA, Moharam ME, Rehim MA. 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-a]pyridine-8-carbonitriles ( QSAR and molecular docking analysis). Egypt Pharmaceut J [serial online] 2012 [cited 2020 Sep 23 ];11:80-92
Available from: http://www.epj.eg.net/article.asp?issn=1687-4315;year=2012;volume=11;issue=2;spage=80;epage=92;aulast=Bassyouni;type=0