Evaluation of 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone (Les-6222) as Potential Anticonvulsant Agent

Abstract

It was determined that the studied 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone (Les-6222) affects the cyclooxygenase pathway of the arachidonic acid cascade, the markers of damage to neurons on models of PTZ kindling. In the model of chronic epileptogenesis in mice (pentylenetetrazole kindling), a 4-thiazolidinone derivative showed high anticonvulsant activity, which is weaker than the effect of sodium valproate and higher than Celecoxib. The mentioned compound has a pronounced anti-inflammatory effect in the brain on the background of the PTZ kindling, reliably inhibiting COX-1 and COX-2. The predominant inhibition of COX-2 by 44.5% indicates this enzyme’s high selectivity of Les-6222. According to the molecular docking study results, the studied compound revealed the properties of COX-1/COX-2 inhibitor and especially 5-LOX/FLAP. The decreasing content of 8-isoprostane in the brain of mice of the Les-6222 group indicates a beneficial effect on cell membranes in the background of oxidative stress during the long-term administration of PTZ. In addition, Les-6222 significantly decreased the content of neuron-specific enolase, indicating neuroprotective properties in the background of chronic epileptogenesis. The obtained results experimentally substantiate the feasibility of further developing Les-6222 as a promising anticonvulsant agent.

Systematic Review on Thiazole Compounds as Nanoparticles: Chemistry, Synthesis, Antimicrobial Activities, Therapeutic Investigation

“…In a study by Vijesh and co-workers [89], a series of 2,4disubstituted thiazole Schiff bases (1) containing pyrazole moiety was synthesized by the Vilsmayer-Haack reaction of appropriate semi-carbazones [90]. All compounds were screened for their antibacterial activities against S.aureus, B.subtilis, E.coli and P.aeruginosa [91].…”

Ameliorative Effect of Ethanolic Extract of Moringa oleifera Leaves in Combination with Curcumin against PTZ-Induced Kindled Epilepsy in Rats: In Vivo and In Silico

“…The brain continuously requires a high oxygen supply and metabolic energy and may be more susceptible than other organs tooxygen species generated during metabolism. Therefore, the consumption of metabolic energy in the central nervous system due to a convulsion state progresses to an oxidative condition in CNS [ 2 ]. There ismuch evidence from clinical and experimental studies thathighlight the involvement of oxidative stress in the development of neurodegenerative diseases [ 3 ].The importance of oxidative stress as an essential mechanism for understanding the seizures caused by epilepsy has been extensively acknowledged.…”