Screening study of new thiazolidinone derivatives for anticonvulsant activity
DOI:
https://doi.org/10.14739/2310-1210.2020.6.218463Keywords:
antiepileptic drugs, epilepsy, thiazolidinone derivativesAbstract
The search for new antiepileptic drugs that would have greater margins of safety and fewer adverse effects is relevant. Thiazolidinone are a promising class for the development of new anticonvulsants.
Aim. To conduct a screening study of new thiazolidinone derivatives for anticonvulsant activity on a seizure model induced by pentylenetetrazole and maximal electroshock; to analyze the structure – activity relationship; to reveal a lead-compound and investigate its dose-dependent manner.
Materials and methods. Basic screening seizure models of pentylenetetrazol and maximal electroshock test were used in mice. The test original 9 thiazolidinone derivatives (100 mg/kg) and the reference drugs of sodium valproate (300 mg/kg), carbamazepine (40 mg/kg) were administered intragastrically 30 minutes before subcutaneous administration of pentylenetetrazol (90 mg/kg) or induction with maximal electroshock by giving a current with strength of 50 mA and frequency of 50 Hz for 0.2 s. In order to study the dose-dependent manner, the lead-compound was administered intragastrically in doses ranging from 25 mg/kg to 150 mg/kg.
Results. A total of 9 compounds were studied, of which 3 did not affect experimental convulsions, 2 showed proconvulsive activity, and 4 had an anticonvulsant effect. The lead-compound 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone was determined under laboratory code Les-6222, which exhibited the highest anticonvulsant properties. The “structure–anticonvulsant activity” relationship in a series of thiazolidinone derivatives was analyzed. The dose-dependent manner of 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone anticonvulsant effect was studied using 2 seizure models, and the most effective dose of 100 mg / kg was identified.
Conclusions. 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylamino)-4-thiazolidinone is a promising compound for in-depth studies on anticonvulsant and related pharmacological activities in order to develop new original anticonvulsants.
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