外链倍半萜内酯:三叶油酯-6- o -异丁酸类似物的设计、合成和抗肝癌评价。

IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL
Xiu-Qiao Zhou, Yi-Ming Qian, Xing Li, Chui-Ji Jiang, Hua-Jie Feng, Hui-Qian He, Hao-Zhe Zeng, Yang Hui, Wen-Hao Chen
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引用次数: 0

摘要

肝细胞癌是一种恶性肿瘤,在全球发病率中排名第六,在全球死亡率中排名第四。本研究基于剪接原理和前药合成策略,以倍半萜内酯外聚物1和2为亲本分子,设计合成了由7个芥菜衍生物和11个胺加合物组成的18个新的倍半萜内酯衍生物。它们的结构通过NMR, hresms和x射线晶体学数据进行了表征。通过CCK8实验,化合物11对HepG2 (IC50 = 4.2 μM)和Huh7 (IC50 = 4.9 μM)细胞的抑制活性最强。随后的药理学实验表明,化合物18可以以时间和剂量依赖的方式降低两种HCC细胞系的活力。化合物11和18在HepG2和Huh7细胞中均能诱导细胞凋亡,阻滞细胞周期进程,抑制细胞增殖和迁移。进一步的转录组分析表明,其中18个具有潜在的抗肿瘤作用。11和18均具有良好的预测ADME和理化性质。总的来说,本研究的发现表明衍生物11和18是治疗肝细胞癌的有希望的候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design, Synthesis, and Anti-Hepatocellular Carcinoma Evaluation Revealed by Transcriptome Analysis of Epimeric Sesquiterpene Lactones: Trilobolide-6-O-isobutyrate Analogues.

Hepatocellular carcinoma is a malignant neoplasm that ranks sixth in global incidence and fourth in global mortality. In this study, based on the splicing principle and prodrug synthesis strategies, a total of 18 new sesquiterpene lactone derivatives, consisting of seven mustard derivatives and 11 amine adducts, were designed and synthesized using the sesquiterpene lactone epimers 1 and 2 as parent molecules. Their structures were characterized by means of NMR, HRESIMS, and X-ray crystallography data. Through the CCK8 assay, compound 11 exhibited the most potent inhibitory activity against HepG2 (IC50 = 4.2 μM) and Huh7 (IC50 = 4.9 μM) cells. Subsequent pharmacological experiments demonstrated that compound 18 could decrease the viability of two HCC cell lines in a time- and dose-dependent manner. Both compounds 11 and 18 were capable of inducing cell apoptosis, arresting the cell cycle progression, and inhibiting cell proliferation and migration in HepG2 and Huh7 cells. Further transcriptome analysis indicated that 18 possessed potential antitumor effects. Both 11 and 18 had favorable predicted ADME and physicochemical properties. Collectively, the findings of this study suggest that derivatives 11 and 18 are promising candidates for the treatment of hepatocellular carcinoma.

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来源期刊
CiteScore
9.10
自引率
5.90%
发文量
294
审稿时长
2.3 months
期刊介绍: The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
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