文章：

天然5Z,9Z-二烯酸的新型合成类似物——基于齐墩果酸的杂合分子：合成与抗肿瘤活性研究

New Synthetic Analogs of Natural 5Z,9Z-Dienoic Acids—Hybrid Molecules Based on Oleanolic Acid: Synthesis and Study of Antitumor Activity

原文发布日期：21 November 2024

DOI: 10.3390/cancers16233893

类型: Article

开放获取: 是

英文摘要：

Objectives: A series of synthetic analogs of natural (5Z,9Z)-diene acids were synthesized for the first time in the form of hybrid molecules containing an oleanolic acid fragment. This fragment was simultaneously linked by an amide bond to various hetero- and carbocyclic amines and a complex ester bond to (5Z,9Z)-tetradeca-5,9-dienecarboxylic acid, which was synthesized by a new reaction of Ti-catalyzed homocyclomagnification of 1,2-dienes.Results: Among the synthesized hybrids, the highest cytotoxic activity was observed for compound9ain the series of Jurkat, K562, U937, and HEK293, with IC50 values of 4.5; 3.1; 2.8; and 26.17 μM/L, respectively. Furthermore, the synthesized compound9ahas been observed to induce apoptosis and exhibit genotoxicity in Jurkat culture, which suggests that it may be a promising candidate for further investigation as an antitumor agent.

摘要翻译： 

目的：本研究首次合成了一系列天然(5Z,9Z)-二烯酸的合成类似物，其结构为含有齐墩果酸片段的杂合分子。该片段通过酰胺键与多种杂环及碳环胺类连接，同时通过复合酯键与(5Z,9Z)-十四碳-5,9-二烯羧酸结合，后者通过钛催化1,2-二烯的新型同环扩增反应合成。 结果：在合成的杂合分子中，化合物9a对Jurkat、K562、U937和HEK293细胞系表现出最强的细胞毒性活性，其IC50值分别为4.5、3.1、2.8和26.17 μM/L。此外，该合成化合物9a被观察到能在Jurkat细胞培养中诱导细胞凋亡并表现出遗传毒性，表明其可能成为具有潜力的抗肿瘤候选药物，值得进一步研究。

原文链接：

New Synthetic Analogs of Natural 5Z,9Z-Dienoic Acids—Hybrid Molecules Based on Oleanolic Acid: Synthesis and Study of Antitumor Activity