Synthesis and anticonvulsant evaluation of indoline derivatives of functionalized aryloxadiazole amine and benzothiazole acetamide

A series of N-(substituted benzothiazole-2-yl)-2-(2,3 dioxoindolin-1-yl)acetamide (4a-i) and substituted-[3-((5-phenyl-1,3,4-oxadiazole-2-yl)imino)indolene-2-one] (5a-f) were designed, synthesized fulfilling the structural requirement of pharmacophore and evaluated for anticonvulsant activities using maximal electroshock test (MES), subcutaneous pentylenetetrazole (scPTZ) seizures and neurotoxicity by motor impairment model in mice. The most active compound N-(5-chlorobenzo[d]thiazol-2-yl)-2-(2,3-dioxoindolin-1-yl)acetamide (4a) has shown significant anticonvulsant activity against both MES and scPTZ screens and emerged as most effective anticonvulsant compound with median dose of 35.7 mg/kg (MES ED50), 88.15 mg/kg (scPTZ ED50) and toxic dose (TD50) was found to be > 500mg/kg. In silico studies including molecular docking study was carried to establish the molecular interaction of potent compound (4a) in both Na+ channel and GABA(A) receptors. The prediction of pharmacokinetic parameters and distance mapping of compounds were also performed to establish the drug likeness property. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

A series of novel anticonvulsant compounds were designed and synthesized, with the most active compound N-(5-chlorobenzo[d]thiazol-2-yl)-2-(2,3-dioxoindolin-1-yl)acetamide (4a) showing significant anticonvulsant activity and potential pharmaceutical value. In silico studies and molecular docking were conducted to investigate the molecular interactions and drug likeness properties of the compounds.