title: Graph theoretical analysis, insilico modeling, design, and synthesis of compounds containing benzimidazole skeleton as antidepressant agents.
abstract: In this study, drug target was identified using KEGG database and network analysis through Cytoscape software. Designed series of novel benzimidazoles were taken along with reference standard Flibanserin for insilico modeling. The novel 4-(1H-benzo[d]imidazol-2-yl)-N-(substituted phenyl)-4-oxobutanamide (3a-j) analogs were synthesized and evaluated for their antidepressant activity. Reaction of 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanoic acid (1) with 4-(1H-benzo [d] imidazol-2-yl)-4-oxobutanoyl chloride (2) furnished novel 4-(1H-benzo [d] imidazol-2-yl)-N-(substituted phenyl)-4-oxobutanamide (3a-j). All the newly synthesized compounds were characterized by IR,1H-NMR, and mass spectral analysis. The antidepressant activities of synthesized derivatives were compared with standard drug clomipramine at a dose level of 20 mg/kg. Among the derivatives tested, most of the compounds were found to have potent activity against depression. The high level of activity was shown by the compounds 3d, 3e, 3i, and it significantly reduced the duration of immobility time at the dose level of 50 mg/kg.
authors: International Research Centre, Kalasalingam University, Krishnankoil, Tamilnadu, India.
authors: Panneerselvam
authors: P
authors: Theivendren
authors: National Centre for Advanced Research in Discrete Mathematics, Kalasalingam University, Krishnankoil, Tamilnadu, India.
authors: Arumugam
authors: A
authors: Subramanian
authors: National Centre for Advanced Research in Discrete Mathematics, Kalasalingam University, Krishnankoil, Tamilnadu, India.
authors: Indhumathy
authors: I
authors: Murugan
authors: Department of Pharmaceutical Chemistry, "SET's" College of Pharmacy, Dharwad, Karnataka, India.
authors: Shrinivas D
authors: SD
authors: Joshi
authors: Department of Pharmaceutical Chemistry, "SET's" College of Pharmacy, Dharwad, Karnataka, India.
authors: Uttam A
authors: UA
authors: More
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D062126:Databases, Chemical; D015195:Drug Design; D051379:Mice; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D045442:Rotarod Performance Test; D023382:Toxicity Tests, Acute
chemical_list: D000928:Antidepressive Agents; D001562:Benzimidazoles; C098107:flibanserin; D008995:Monoamine Oxidase
keywords: antidepressant activity; benzimidazoles; docking studies; graph theoretical analysis; spectral analysis