5,6-Dihydropyrimidine-1(2H)-carbothioamides: Synthesis, in vitro GABA-AT screening, anticonvulsant activity and molecular modelling study.
Bioorg Chem
; 77: 56-67, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29331765
ABSTRACT
Even after considerable advances in the field of epilepsy treatment, convulsions are inefficiently controlled by standard drug therapy. Herein, a series of pyrimidine-carbothioamide derivatives 4(a-t) was designed as anticonvulsant agents by doing some important structural modifications in well-known anticonvulsant drugs. Two classical animal models were used for the in vivo anticonvulsant screening, maximum electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models; followed by motor impairment study by rotarod method. The most active compound 4g effectively suppressed seizure effect in both the animal models with median doses of 15.6â¯mg/kg (MES ED50), 278.4â¯mg/kg (scPTZ ED50) and 534.4â¯mg/kg (TD50) with no sign of neurotoxicity. Furthermore, in vitro GABA-AT enzyme activity assay of 4g showed inhibitory potency (IC50) of 12.23⯵M. The docking study also favored the animal studies.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Convulsões
/
Tioamidas
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Inibidores Enzimáticos
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4-Aminobutirato Transaminase
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Anticonvulsivantes
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Índia