Design, synthesis and biological evaluation of novel urolithin derivatives targeting liver cancer cells.

IF 5.6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-15 DOI:10.1080/14756366.2025.2490707

Mi Tian, Lirong Zhao, Yu Lan, Chen Li, Yipeng Ling, Benhong Zhou

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Abstract

We designed and synthesised 22 new urolithin derivatives (UDs) based on methyl-urolithin A (mUA) to identify anti-cancer drugs with high efficacy and low toxicity and evaluated their anti-cancer activities in vitro. Cytotoxicity tests were performed on three cell lines (DU145, T24, and HepG2) and a human normal cell line (HK-2). The half-inhibitory concentration (IC₅₀) of derivative UD-4c to hepatoma HepG2 cells (IC₅₀ = 4.66 ± 0.12 μM) was significantly lower than that of sorafenib (IC₅₀ =7.76 ± 0.12 μM), and exhibited less toxicity to HK-2 cells. Preliminary studies on the mechanism revealed that the derivative UD-4c could significantly inhibit the HepG2 cell growth and colony formation, block the HepG2 cell cycle in the G2/M phase, and induce apoptosis of HepG2 cells dose-dependently. The derivative UD-4c can be used as a potential lead compound to further develop new drugs for hepatocellular carcinoma treatment based on the evaluation of anti-cancer activity.

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针对肝癌细胞的新型尿素衍生物的设计、合成及生物学评价。

设计合成了22种基于甲基尿素A （mUA）的新型尿素衍生物（UDs），以鉴定高效、低毒的抗癌药物，并对其体外抗癌活性进行了评价。对3株细胞系（DU145、T24和HepG2）和1株人正常细胞系（HK-2）进行细胞毒性试验。d -4c衍生物对肝癌HepG2细胞的半抑制浓度（IC50 = 4.66±0.12 μM）明显低于索拉非尼（IC50 =7.76±0.12 μM），对HK-2细胞的毒性较小。初步机制研究发现，其衍生物UD-4c能显著抑制HepG2细胞生长和集落形成，阻断HepG2细胞周期在G2/M期，并能剂量依赖性地诱导HepG2细胞凋亡。衍生物UD-4c可作为潜在先导化合物，在抗癌活性评价的基础上进一步开发治疗肝细胞癌的新药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Enzyme Inhibition and Medicinal Chemistry 医学-生化与分子生物学

CiteScore

10.30

自引率

10.70%

发文量

195

审稿时长

4-8 weeks

期刊介绍： Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.