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新型抗惊厥候选药物5-（3-氯苯基）-4-己基-2,4-二氢-3H-1,2,4-三唑-3-硫酮的作用分子机制及安全性

Molecular mechanism of action and safety of 5-(3-chlorophenyl)-4-hexyl-2,4-dihydro-3-1,2,4-triazole-3-thione - a novel anticonvulsant drug candidate.

作者信息

Kaproń Barbara, Łuszczki Jarogniew, Paneth Agata, Wujec Monika, Siwek Agata, Karcz Tadeusz, Mordyl Barbara, Głuch-Lutwin Monika, Gryboś Anna, Nowak Gabriel, Pająk Karolina, Jóźwiak Krzysztof, Tomczykowski Adam, Plech Tomasz

机构信息

Department of Organic Chemistry, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Poland.

Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, Lublin 20-090, Poland.

出版信息

Int J Med Sci. 2017 Jul 18;14(8):741-749. doi: 10.7150/ijms.20001. eCollection 2017.

DOI:10.7150/ijms.20001
PMID:28824309
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5562128/
Abstract

Previously, it was found that 5-(3-chlorophenyl)-4-hexyl-2,4-dihydro-3-1,2,4-triazole-3-thione (TP-315) effectively protects mice from maximal electroshock-induced seizures. The aim of this study was to determine possible interactions between TP-315 and different molecular targets, i.e. GABA receptors, voltage-gated sodium channels, and human neuronal α7 and α4β2 nicotinic acetylcholine receptors. The influence of TP-315 on the viability of human hepatic HepG2 cells was also established using PrestoBlue and ToxiLight assays. It was found that the anticonvulsant activity of TP-315 results (at least partially) from its influence on voltage-gated sodium channels (VGSCs). Moreover, the title compound slightly affected the viability of human hepatic cells.

摘要

此前发现，5-(3-氯苯基)-4-己基-2,4-二氢-3H-1,2,4-三唑-3-硫酮(TP-315)能有效保护小鼠免受最大电休克诱导的癫痫发作。本研究的目的是确定TP-315与不同分子靶点之间可能的相互作用，即γ-氨基丁酸(GABA)受体、电压门控钠通道以及人类神经元α7和α4β2烟碱型乙酰胆碱受体。还使用PrestoBlue和ToxiLight检测法确定了TP-315对人肝癌HepG2细胞活力的影响。结果发现，TP-315的抗惊厥活性（至少部分）源于其对电压门控钠通道(VGSCs)的影响。此外，该标题化合物对人肝细胞活力有轻微影响。

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