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laurequinone,一种针对. 的先导化合物

Laurequinone, a Lead Compound against .

机构信息

Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.

Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.

出版信息

Mar Drugs. 2023 May 30;21(6):333. doi: 10.3390/md21060333.

Abstract

Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga have been studied for this purpose. The different compounds were tested in vitro against the promastigote and amastigote forms of . Different assays were also performed, including the measurement of mitochondrial potential, determination of ROS accumulation, and chromatin condensation, among others, focused on the detection of the cell death process known in this type of organism as apoptosis-like. Five compounds were identified that displayed leishmanicidal activity: laurequinone, laurinterol, debromolaurinterol, isolaurinterol, and aplysin, showing IC values against promastigotes of 1.87, 34.45, 12.48, 10.09, and 54.13 µM, respectively. Laurequinone was the most potent compound tested and was shown to be more effective than the reference drug miltefosine against promastigotes. Different death mechanism studies carried out showed that laurequinone appears to induce programmed cell death or apoptosis in the parasite studied. The obtained results underline the potential of this sesquiterpene as a novel anti-kinetoplastid therapeutic agent.

摘要

在被忽视的热带病中,利什曼病不仅是导致死亡的主要原因之一,也是导致残疾调整生命年的主要原因之一。这种疾病是由原生动物寄生虫引起的,可引发不同的临床表现,包括皮肤、黏膜和内脏形式。由于现有的寄生虫病治疗方法对患者不够有效或安全,因此在这项工作中,我们研究了从红藻中分离出的不同倍半萜类化合物,以达到这一目的。不同的化合物在体外对前鞭毛体和无鞭毛体形式的进行了测试。还进行了不同的测定,包括线粒体电位测量、ROS 积累测定、染色质浓缩等,旨在检测这种生物类型中称为凋亡样的细胞死亡过程。有 5 种化合物被鉴定具有杀利什曼原虫活性:laurequinone、laurinterol、debromolaurinterol、isolaurinterol 和 aplysin,对前鞭毛体的 IC 值分别为 1.87、34.45、12.48、10.09 和 54.13µM。laurequinone 是测试的最有效化合物,对前鞭毛体的效果优于参考药物米替福新。进行的不同死亡机制研究表明,laurequinone 似乎诱导研究寄生虫中的程序性细胞死亡或细胞凋亡。研究结果强调了这种倍半萜作为新型抗锥虫治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa1/10304164/4cb9d6e80923/marinedrugs-21-00333-g001.jpg

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