Synthesis and anticonvulsant activities of novel 2-(cyclopentylmethylene)hydrazinyl-1,3-thiazoles in mouse models of seizures

J Enzyme Inhib Med Chem. 2016 Dec;31(6):1576-82. doi: 10.3109/14756366.2016.1158172. Epub 2016 Apr 6.

Abstract

Synthesis, characterization and investigation of in vivo anticonvulsant activities of 13 novel cyclopentanecarbaldehyde-based 2,4-disubstituted 1,3-thiazoles are presented. Their structures were determined using (1)H and (13)C NMR, FAB(+)-MS, HRMS and elemental analyses. The results of anticonvulsant screening reveal that seven intraperitoneally administered compounds: 3a, 3b, 3d, 3e, 3f, 3k and 3m containing F-, Cl-, Br-, CF3-, CH3- and adamantyl substituents demonstrated significant anticonvulsant activity in the pentylenetetrazole model with median effective doses (ED50) ≤ 20 mg/kg, respectively, which was approximately seven-fold lower than that reported for the reference drug, ethosuximide. Noteworthy, none of these compounds impaired animals' motor skills in the rotarod test.

Keywords: Anticonvulsant drugs; PTZ model; epilepsy; rotarod test; thiazoles.

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / pharmacology*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Disease Models, Animal*
  • Male
  • Mass Spectrometry / methods
  • Mice
  • Pilocarpine / administration & dosage
  • Proton Magnetic Resonance Spectroscopy
  • Rotarod Performance Test
  • Seizures / prevention & control*
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology*

Substances

  • Anticonvulsants
  • Thiazoles
  • Pilocarpine