title: Synthesis of benzimidazole based thiadiazole and carbohydrazide conjugates as glycogen synthase kinase-3β inhibitors with anti-depressant activity.
abstract: A series of benzimidazole based thiadiazole and carbohydrazide conjugates have been synthesized and evaluated for inhibition of glycogen synthase kinase-3β and anti-depressant effect. Compounds 4f, 4j, 5b, 5g and 5i were found to be the most potent inhibitors of GSK-3β in vitro amongst the twenty-five benzimidazole based thiadiazole and carbohydrazide conjugates synthesized. Compound 5i was also found to exhibit significant antidepressant activity in vivo at 50mg/kg, when compared to fluoxetine, a known antidepressant drug. The molecular docking studies revealed multiple hydrogen bond interactions by the synthesized compounds with various amino acid residues, viz, ASP-133, LYS-183, PRO-136, VAL-135, TYR-134, or LYS-60 at the GSK-3β receptor site.
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Mushtaq A
authors.initials: MA
authors.lastname: Tantray
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: hhamid@jamiahamdard.ac.in.
authors.forename: Hinna
authors.initials: H
authors.lastname: Hamid
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Mohammad Sarwar
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Abul
authors.initials: A
authors.lastname: Kalam
authors.affiliation: CSIR Unit for Research and Development of Information Products, Pune 411038, India.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Dhulap
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006834:Hydrazines / Q000737:chemistry; D006860:Hydrogen Bonding; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013830:Thiadiazoles / Q000737:chemistry
chemical_list: D014150:Antipsychotic Agents; D001562:Benzimidazoles; D006834:Hydrazines; D013830:Thiadiazoles; C031000:benzimidazole; D000071679:Glycogen Synthase Kinase 3 beta; C019289:carbohydrazide
keywords: Benzimidazole; Carbohydrazide; Glycogen synthase kinase; Molecular docking; Thiadiazole