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Arch Pharm (Weinheim) ; 347(10): 756-67, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25059811

RESUMO

Two series of novel indolyl thiazolidin-4-one derivatives 4a-j and 5a-j were obtained by an ecofriendly synthetic protocol by treating a mixture of Schiff's bases (0.01 mol) with thioglycolic acid or thiolactic acid (0.01 mol) and anhydrous zinc chloride in catalytic amount in DMF as solvent under ultrasound irradiation, using an ultrasound synthesizer with a synthetic solid probe. The structures of the synthesized compounds were confirmed by IR, (1) H NMR, (13) C NMR, MS, and elemental analysis. The anticonvulsant activity and neurotoxicity of the newly synthesized compounds were established by MES and sc-PTZ model and by rotarod test, respectively, in vivo using mouse models. The actophotometer was used for the screening of behavioral activity. The compounds exhibited promising anticonvulsant activity; especially, the compounds showed maximum protection in the MES model at a dose of 100 mg/kg. Further, docking studies of the synthesized compounds were performed against the sodium channel receptor and showed good binding interactions with the receptor. A computational study was carried out to highlight the pharmacophore distance mapping, log p determination, and pharmacokinetic parameters.


Assuntos
Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Desenho de Fármacos , Indóis/síntese química , Indóis/farmacologia , Convulsões/prevenção & controle , Tiazolidinas/síntese química , Tiazolidinas/farmacologia , Ultrassom , Animais , Anticonvulsivantes/toxicidade , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Eletrochoque , Indóis/toxicidade , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/psicologia , Pentilenotetrazol , Teste de Desempenho do Rota-Rod , Convulsões/etiologia , Convulsões/fisiopatologia , Relação Estrutura-Atividade , Tiazolidinas/toxicidade , Fatores de Tempo
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