5,6-Dihydropyrimidine-1(2H)-carbothioamides: Synthesis, in vitro GABA-AT screening, anticonvulsant activity and molecular modelling study.
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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 15.6 mg/kg (MES ED50), 278.4 mg/kg (scPTZ ED50) and 534.4 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 μM. The docking study also favored the animal studies. |
Year of Publication | :
2018
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Journal | :
Bioorganic chemistry
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Volume | :
77
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Number of Pages | :
56-67
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Date Published | :
2018
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ISSN Number | :
0045-2068
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URL | :
http://linkinghub.elsevier.com/retrieve/pii/S0045-2068(17)30851-9
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DOI | :
10.1016/j.bioorg.2017.12.031
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Short Title | :
Bioorg Chem
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