| 冯贝贝,许嘉琛,刘成波,何黎琴.化学通报,2026,89(4):424-432. |
| 芦荟大黄素哌嗪衍生物的设计、合成和抗肿瘤活性研究 |
| Design, synthesis and biological evaluation of aloe emodin piperazine derivatives as anti-tumor agents |
| 投稿时间：2025-12-13 修订日期：2026-01-31 |
| DOI： |
| 中文关键词: 芦荟大黄素 15-哌嗪芦荟大黄素 香豆素 抗癌活性 |
| 英文关键词:Aloe emodin 15-(piperazinyl-1) aloe emodin Coumarin anticancer activity |
| 基金项目:安徽省高校科研项目(2020AH051980)资助 |
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| 中文摘要: |
| 芦荟大黄素是传统中药大黄的主要活性成分之一。研究表明,芦荟大黄素具有一定的抗肿瘤活性,但其活性不强,水溶性低,影响其临床应用。本研究基于药效基团拼接原理,在芦荟大黄素的15-位引入亲水性基团哌嗪后再与具有抗肿瘤活性的药效团香豆素偶联,设计并合成了10个结构新颖的芦荟大黄素哌嗪衍生物。目标化合物的结构通过1H NMR、13C NMR和HR-MS 等方法进行了表征。采用MTT法评价了目标化合物对四种不同肿瘤细胞(HeLa、HepG-2、U2OS和A549)的体外抗增殖活性。结果显示,目标化合物对测试的肿瘤细胞均具有较强的细胞增殖抑制作用。其中化合物6g具有显著的抗骨肉瘤活性,IC50为3.37 μM,且对正常肝细胞THLE-2影响较小(IC50为18.11 μM),显示出良好的选择性。进一步的研究表明,化合物6g可诱导U2OS细胞凋亡。体外羟基磷灰石吸附实验表明,化合物6g具有良好的骨亲和性。本研究表明,通过对芦荟大黄素进行结构修饰可以获得具有开发前景的抗骨肉瘤先导化合物。 |
| 英文摘要: |
| Aloe emodin is one of the main active constituents of the traditional Chinese medicine rhubarb. A recent study showed that aloe-emodin can induce apoptosis in human tumor cells. However, the clinical application of aloe-emodin has been hampered by its low anti-tumor activity and poor aqueous solubility. Based on the pharmacophore fusion strategy, ten novel aloe-emodin piperazine coumarin conjugates were designed and synthesized. The structures of the target compounds were characterized by 1H NMR, 13C NMR, and HR?MS. Their in vitro anticancer activity against four human cancer cell lines (HeLa, HepG?2, U2OS, and A549) was evaluated using the MTT assay. The results showed that all target compounds exhibited potent inhibitory effects against the tested tumor cells. Among them, compound6gdisplayed significant anti?osteosarcoma activity with an IC50 of 3.37?μM and showed low cytotoxicity for the normal liver epithelial THLE-2 cells (IC50?=?18.11?μM). Further studies revealed that compound6gcould induce apoptosis in U2OS cells. In vitro hydroxyapatite adsorption experiments demonstrated that compound6gpossesses favorable bone affinity. The results show that a promising lead compound for anti-osteosarcoma can be obtained by modifying the structure of aloin emodin. |
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