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

IF 2.3 Q3 PHARMACOLOGY & PHARMACY Scientia Pharmaceutica Pub Date : 2022-09-19 DOI:10.3390/scipharm90030056
M. Mishchenko, S. Shtrygol’, A. Lozynskyi, Mykhailo Hoidyk, Dmytro Khyluk, T. Gorbach, R. Lesyk
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引用次数: 2

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.
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5-[(Z)-(4-硝基苄基)]-2-(噻唑-2-ylimino)-4-噻唑烷酮(Les-6222)作为潜在抗惊厥剂的评价
确定所研究的5-[(Z)-(4-硝基亚苄基)]-2-(噻唑-2-基氨基)-4-噻唑烷酮(Les-6222)影响花生四烯酸级联的环氧合酶途径,花生四烯酸是PTZ点燃模型上神经元损伤的标志物。在小鼠慢性癫痫发生模型(戊四唑点燃)中,一种4-噻唑烷酮衍生物显示出高的抗惊厥活性,该活性弱于丙戊酸钠,高于塞来昔布。上述化合物在PTZ点燃的背景下在大脑中具有显著的抗炎作用,可靠地抑制COX-1和COX-2。对COX-2的主要抑制率为44.5%,表明该酶对Les-6222具有高选择性。根据分子对接研究结果,所研究的化合物揭示了COX-1/COX-2抑制剂,尤其是5-LOX/FLAP的特性。Les-6222组小鼠大脑中8-异丙肾上腺素含量的降低表明在长期给予PTZ期间,在氧化应激的背景下对细胞膜有有益的影响。此外,Les-6222显著降低了神经元特异性烯醇化酶的含量,表明在慢性癫痫发生背景下具有神经保护特性。实验结果证实了进一步开发Les-6222作为一种有前景的抗惊厥剂的可行性。
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来源期刊
Scientia Pharmaceutica
Scientia Pharmaceutica Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.60
自引率
4.00%
发文量
67
审稿时长
10 weeks
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