生物反应和细胞死亡信号通路由人体细胞中以四化基素为基础的aldoximes调节

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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Antonio Zandona¹, Josip Madunić¹, Katarina Miš²

¹Institute for Medical Research and Occupational Health, POB 291, HR-10001 Zagreb, Croatia.

|July 7, 2023

概括

某些阿尔多克西姆药物没有毒性,而另一些药物则会触发亡并影响新陈代谢,这表明除了有机酸盐中毒的解毒剂之外还有潜在的用途.

科学领域:

生物化学生物化学
毒理学毒理学毒理学
细胞生物学细胞生物学

背景情况:

作为对有机酸盐 (OP) 中毒的解药,3-基-2-氨酸阿尔多克西姆正在研究中.
结构特征表明,除了OP抗毒剂应用之外,还存在潜在的生物活动.

研究的目的:

评估特定的阿尔多克西姆对人类细胞的基于细胞的作用和作用机制.
评估这些化合物的安全性和潜在的治疗应用.

主要方法:

使用人类细胞系 (SH-SY5Y,HEK293,HepG2,HK-2,肌细胞,肌管) 进行了广泛的基于细胞的测试.
对亡途径 (ERK1/2,p38-MAPK,caspases),DNA损伤和代谢影响的分析.
在分析,包括酶标预测和药模拟.

主要成果:

含有piperidine的aldoximes在24小时内没有显示出高达300μM的显著毒性.
含有四化素的阿尔多克西姆通过内在途径诱导了依赖时间的亡,影响了线粒体和脂肪酸代谢.
在 silico 研究中预测了激酶和细胞染色体P450cam作为潜在的目标.

结论:

皮皮瑞丁阿尔多克西姆需要进一步调查,作为潜在的医疗对策.
甲基化氨酸阿尔多克西姆表现出显著的生物活性,这表明有可能设计用于癌症等疾病的新疗法,或作为OP抗毒剂设计中的负调节剂.

关键词:

抗毒剂的抗剂是什么?细胞灭亡 (apoptosis) 是一种死亡的过程.细胞活力细胞活力氧化物是氧化物中的一种.药科类动物 (Pharmacophore) 是一种药科类动物.

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