Toxicologie : accès libre

Abstrait

Novel Benzo[d]thiazole with Dimethylpyrazol Derivatives: Design, Synthesis and Biological Evaluation

Dachuan Liu, Xiu Cheng, Ying Wang and Chenzhu Wu

A series of new benzothiazole derivatives containing dimethylpyrazole were synthesized and evaluated for their anticonvulsant activity, neurotoxicity and cytotoxicity by using the maximal electroshock (MES), rotarod neurotoxicity (TOX) and MTT colorimetric assay. Among the compounds studied, four compounds (6a, 6b, 6g and 6m) showed better anticonvulsant than the others. All the synthetic compounds showed lower neurotoxicity and little cytotoxicity, so that the compounds with better activities also had higher protective index.In particular, the compound 6g, 2-(3,5- dimethyl-1H-pyrazol-1-yl)-6-((2-fluorobenzyl)oxy)benzo[d]thiazole showed better activity with an ED50 value of 160.4 mg/kg and higher protective index (PI) values of 2.74 in the MES test than the standard drugs used as positive controls in this study. Then the compound 6g demonstrated antagonistic activity against seizures induced by pentylenetetrazol, which proved 6g maybe exert activity through effecting GABAergic neurotransmission.