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氰基丙烯酰胺和 5-亚氨基吡咯-2-酮的合成及生物评价

Synthesis and Biological Evaluation of Cyanoacrylamides and 5-Iminopyrrol-2-Ones Against .

机构信息

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, Islas Canarias 38203, Spain.

Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, La laguna, Tenerife, Islas Canarias 38200, Spain.

出版信息

ACS Infect Dis. 2024 Sep 13;10(9):3332-3345. doi: 10.1021/acsinfecdis.4c00439. Epub 2024 Aug 8.

DOI:10.1021/acsinfecdis.4c00439
PMID:39116454
Abstract

Primary amoebic meningoencephalitis is caused by the free-living amoeba . The lack of standardized treatment has significantly contributed to the high fatality rates observed in reported cases. Therefore, this study aims to explore the anti- activity of eight synthesized cyanoacrylamides and 5-iminopyrrol-2-ones. Notably, QOET-109, QOET-111, QOET-112, and QOET-114 exhibited a higher selectivity index against compared to those of the rest of the compounds. Subsequently, these chemicals were assessed against the resistant stage of , demonstrating activity similar to that observed in the vegetative stage. Moreover, characteristic events of programmed cell death were evidenced, including chromatin condensation, increased plasma membrane permeability, mitochondrial damage, and heightened oxidative stress, among others. Finally, this research demonstrated the activity of the cyanoacrylamide and 5-iminopyrrol-2-one molecules, as well as the induction of metabolic event characteristics of regulated cell death in .

摘要

原发性阿米巴脑膜脑炎是由自由生活的阿米巴引起的。缺乏标准化的治疗方法显著导致了报告病例中观察到的高死亡率。因此,本研究旨在探索八种合成的氰基丙烯酰胺和 5-亚氨基吡咯-2-酮的抗活性。值得注意的是,与其他化合物相比,QOET-109、QOET-111、QOET-112 和 QOET-114 对的选择性指数更高。随后,这些化学物质被评估对的抗性阶段,表现出与营养阶段相似的活性。此外,还证实了程序性细胞死亡的特征事件,包括染色质浓缩、质膜通透性增加、线粒体损伤和氧化应激加剧等。最后,本研究证明了氰基丙烯酰胺和 5-亚氨基吡咯-2-酮分子的活性,以及诱导中调节细胞死亡的代谢事件特征。

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