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新冠盒状分子的杀阿米巴作用:细胞死亡研究

Amoebicidal Effect of COVID Box Molecules against : A Study of Cell Death.

作者信息

Sifaoui Ines, Rodríguez-Expósito Rubén L, Reyes-Batlle María, Sutak Robert, Piñero José E, Lorenzo-Morales Jacob

机构信息

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, S/N, 38200 San Cristóbal de La Laguna, Spain.

Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, Spain.

出版信息

Pharmaceuticals (Basel). 2024 Jun 20;17(6):808. doi: 10.3390/ph17060808.

Abstract

spp. can cause a sight threatening disease. At present, the current treatments used to treat spp. Infections, such as biguanide-based antimicrobials, remain inefficacious, with the appearance of resistant forms and high cytotoxicity to host cells. In this study, an initial screening was conducted against Neff and murine macrophages J774A.1 using alamarBlue™. Among the 160 compounds included in the cited box, 90% exhibited an inhibition of the parasite above 80%, while only 18.75% of the compounds inhibited the parasite with a lethality towards murine macrophage lower than 20%. Based on the amoebicidal activity, the cytotoxicity assay, and availability, Terconazole was chosen for the elucidation of the action mode in two clinical strains, and L10. A fluorescence image-based system and proteomic techniques were used to investigate the effect of the present azole on the cytoskeleton network and various programmed cell death features, including chromatin condensation and mitochondria dysfunction. Taking all the results together, we can suggest that Terconazole can induce programmed cell death (PCD) via the inhibition of sterol biosynthesis inhibition.

摘要

某些物种可引发威胁视力的疾病。目前,用于治疗某些物种感染的现有疗法,如基于双胍的抗菌药物,仍然无效,出现了耐药形式且对宿主细胞具有高细胞毒性。在本研究中,使用alamarBlue™对Neff和小鼠巨噬细胞J774A.1进行了初步筛选。在所引用方框中的160种化合物中,90%对寄生虫的抑制率高于80%,而只有18.75%的化合物对寄生虫具有致死性,且对小鼠巨噬细胞的致死率低于20%。基于杀阿米巴活性、细胞毒性测定以及可用性,选择了特康唑来阐明其在两种临床菌株和L10中的作用模式。使用基于荧光图像的系统和蛋白质组学技术来研究该唑类药物对细胞骨架网络以及各种程序性细胞死亡特征的影响,包括染色质浓缩和线粒体功能障碍。综合所有结果,我们可以认为特康唑可通过抑制甾醇生物合成来诱导程序性细胞死亡(PCD)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/11206913/95843b63cea9/pharmaceuticals-17-00808-g001.jpg

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