title: Synthesis, Biological Activity, and Docking Study of Novel Isatin Coupled Thiazolidin-4-one Derivatives as Anticonvulsants.
abstract: A series of 2-(substituted-phenyl)-3-(2-oxoindolin-3-ylidene)amino)-thiazolidin-4-one derivatives were designed and synthesized under microwave irradiation, using an eco-friendly, efficient, microwave-assisted synthetic protocol that involves cyclocondensation of 3-substituted benzylidine-hydrazono-indolin-2-one 3a-j with thioglycolic acid in dimethyl formamide (DMF) as solvent and anhydrous zinc chloride as a catalyst, keeping in view the structural requirement of the pharmacophore. The intermediate compounds 3a-j were obtained by condensation of the hydrazone of indoline-2,3-dione with aromatic aldehydes. The synthesized derivatives were evaluated for CNS depressant activity and anticonvulsant activity in mice using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) induced seizure tests. All the derivatives showed good CNS depressant activity and showed protection in the MES test, indicative of their ability to inhibit the seizure spread. A histopathological study was performed to evaluate liver toxicity caused by the synthesized compounds. The compounds were nontoxic. A computational study was performed, in which log P values were calculated experimentally. Virtual screening was performed by molecular docking of the designed compounds into the ATP binding sites of the NMDA and AMPA receptors, to predict if these compounds have analogous binding modes.
authors.affiliation: Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Nikalje
authors.affiliation: Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India.
authors.forename: Altamash
authors.initials: A
authors.lastname: Ansari
authors.affiliation: Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmacy, Shirpur (Dhule), Maharashtra, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bari
authors.affiliation: Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmacy, Shirpur (Dhule), Maharashtra, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Ugale
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D017076:Computer-Aided Design; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D007510:Isatin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010433:Pentylenetetrazole; D011485:Protein Binding; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism; D012640:Seizures / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D008024:Ligands; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D053778:Thiazolidines; D007510:Isatin; D010433:Pentylenetetrazole
keywords: Anticonvulsants; Indoline-2,3-dione; MES test; Molecular docking; PTZ-induced seizure