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.

<strong>Microwave-Assisted Facile Synthesis and anticonvulsant evaluation of Novel </strong><strong>N-(3-chloro-2-oxo-4-substituted phenyl azetidin-1-yl)-2-(1, 3-dioxoisoindolin-2-yl) acetamides</strong>

“…On the basis of the above findings from literature survey and considering the need for the development of potent CNS active agents, in continuation to our earlier efforts in finding better, novel anticonvulsant agents [21][22][23][24] it was thought worthwhile to synthesize heterocyclic system containing phthalimide and azetidinone ring to give coupled derivatives having more potent anticonvulsant activity.…”

Synthesis, molecular modeling studies, and anticonvulsant evaluation of novel 1‐((2‐hydroxyethyl)(aryl)amino)‐N‐substituted cycloalkanecarboxamides and their acetate esters

“…In addition, the generated hypothetical pharmacophore model was presented in Figure , which might be responsible for interface with the receptor active site. Distances and angles between the pharmacophoric features of the training sets (A, HBA, HY) are shown in Table …”

Pre‐clinical evidence of safety and protective effect of isatin and oxime derivatives against malathion‐induced toxicity

“…52 Isatin is an endogenous compound present in plants and human beings. 53 The biological properties of isatin and its derivatives include antibacterial, 54,55 anticonvulsant, 56 antidepressant 57 and anti-inflammatory activities. 58 In agreement with this, isatin and its derivatives also seem to have low toxicity.…”