Effects of 4-Thiazolidinone Derivatives Les-2658 and Les-1205 on Sleep - Wakefulness Cycle in Kindled Rats

Abstract

The research is dedicated to in-depth study of neurotrophic and antiepileptic properties of original potential anticonvulsant agents from 4-thiazolidinones – LES-2658 (5-(3-nitro-benzylidene)-2-(thiazol-2-ylimino)-thiazolidin-4-one) and LES-1205 ([2,4-dioxo-5-(thiazol-2-ylcarbamoylmethyl)-thiazolidin-3-yl]-acetic acid ethyl ester), synthesized at the Department of Pharmaceutical, Organic and Bioorganic Chemistry of Danylo Halytsky Lviv National Medical University, Ukraine. Studying of sleep - wakefulness cycle characteristics in animals with chronic epileptic syndrome in conditions of 4-thiazolidinones derivatives LES-2658 and LES-1205 use was performed. The kindling syndrome was induced in Wistar rats via daily pentylenetetrazol (PTZ) (30 mg/kg, i.p.) administrations during three weeks and sleep - wakefulness cycle was studied under conditions of LES-2658 and LES-1205 administrations at doses 25.0and 100.0 mg/kg i.p.. Total wakefulness, non - rapid eye movement sleep, rapid eye movement sleep, falling asleep latency, REM - onset latency and also number of REM sleep episodes have been determined by behavioral characteristics of experimental animals. It was established that 4-thiazolidinone derivatives Les-1205 and Les-2658 reduce REM sleep fragmentation and increase its duration in PTZ-kindled rats. Les-1205 compound at dose 100.0 mg/kg show a clear correcting influence on kindling - induced sleep disturbances.

Thiazole-Bearing 4-Thiazolidinones as New Anticonvulsant Agents

“…The design of molecule structure of target compounds was based on: Our former findings [22,39]; the compliance with structural requirements for potential anticonvulsants (see above); combination of thiazole and thiazolidinone cores in one molecule [49,50]; structural similarity with ralitolin ( Figure 2). Target compounds belong to the two 4-thiazolidinone subtypes-2-imino-4-thiazolidinones I and 5-carboxymethyl(idene)-2,4-thiazolidinediones II.…”

“…The present work is an extension of our ongoing efforts towards a search for new 4-thiazolidinone-based anticonvulsant agents [22,39]. Here, we addressed the design and synthesis of thiazole-thiazolidinones hybrids and evaluation of their anticonvulsant effects.…”