5,6-Dihydropyrimidine-1(2H)-carbothioamides: Synthesis, in vitro GABA-AT screening, anticonvulsant activity and molecular modelling study
| Autor: | Sharad Wakode, Vidushi Sharma, Nadeem Siddiqui, Meeta Sahu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Models Molecular medicine.medical_treatment Drug Evaluation Preclinical Pharmacology 01 natural sciences Biochemistry Rotarod performance test 03 medical and health sciences Mice Structure-Activity Relationship In vivo Seizures Drug Discovery medicine Animals Enzyme Inhibitors Molecular Biology Electroshock Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Neurotoxicity medicine.disease In vitro 0104 chemical sciences Thioamides Anticonvulsant Agent 030104 developmental biology Anticonvulsant Pyrimidines Docking (molecular) 4-Aminobutyrate Transaminase Pentylenetetrazole Anticonvulsants Animal studies |
| Zdroj: | Bioorganic chemistry. 77 |
| ISSN: | 1090-2120 |
| Popis: | 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 15.6 mg/kg (MES ED 50 ), 278.4 mg/kg (scPTZ ED 50 ) and 534.4 mg/kg (TD 50 ) with no sign of neurotoxicity. Furthermore, in vitro GABA-AT enzyme activity assay of 4g showed inhibitory potency (IC 50 ) of 12.23 μM. The docking study also favored the animal studies. |
| Databáze: | OpenAIRE |
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