作为潜在癌症抑制剂的松脂酸骨架衍生物的设计、合成和体外生物活性

IF 1.2 4区医学 Q4 CHEMISTRY, MEDICINAL

Letters in Drug Design & Discovery Pub Date : 2024-04-17 DOI:10.2174/0115701808300981240408063655

Bin Zhou, Lisheng Wang, Yongquan Wei, Meiyan Jiang, Xingdong Wang

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引用次数: 0

摘要

背景：以优秀的先导化合物 Matrine 为基础，设计并合成了 13 种衍生物。研究目的本研究旨在发现具有卓越抗癌活性的新型抗癌剂，并为新药的发现提供支持。研究方法采用 MTT 法测定所有衍生物对 A549、HGC-27、HCT-116 和 HeLa 四种人类癌细胞的体外抗增殖活性。对最佳活性化合物进行细胞克隆、迁移、细胞周期和凋亡以及分子对接。结果显示化合物 5XI 对所有四种细胞株均表现出最佳活性，尤其是对 A549 细胞，其 IC50 为 5.805 μmol/L。5XI 的抗增殖活性远高于马钱子碱，仅略低于多靶点小分子抑制剂顺铂。5XI 还在细胞周期、细胞凋亡、细胞划痕和细胞克隆试验中表现出优异的抑制活性，并在对接研究中显示出良好的亲和性。结论：5XI 具有优异的抗增殖活性，能显著抑制细胞克隆和迁移，影响癌细胞周期分布，并以浓度依赖性方式诱导细胞凋亡，是一种潜在的抗癌药物。

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Design, Synthesis, and In vitro Biological Activities of Matrine Skeleton Derivatives as Potential Cancer Inhibitors

Background: Thirteen derivatives were designed and synthesized based on the excellent lead compound Matrine. Objective: This study aimed to discover novel anticancer agents with superior anticancer activity and to support the discovery of new drugs. Methods: The in vitro antiproliferative activity of all derivatives against four human cancer cells, A549, HGC-27, HCT-116, and HeLa, was determined by MTT. The best active compounds were subjected to cell cloning, migration, cell cycle and apoptosis, and molecular docking. Results: Compound 5XI showed the best activity against all four cell lines, especially against A549 cells, with an IC50 of 5.805 μmol/L. The antiproliferative activity of 5XI was much higher than that of matrine and only slightly weaker than that of Cisplatin, a multi-targeted small molecule inhibitor. 5XI also showed excellent inhibitory activity in cell cycle, apoptosis, cell scratch, and cell cloning assays and has shown good affinity in docking studies. Conclusion: 5XI has excellent antiproliferative activity, significantly inhibits cell cloning and migration, affects cancer cell cycle distribution, and induces apoptosis in a concentration-dependent manner, making it a potential anticancer drug agent.

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来源期刊

Letters in Drug Design & Discovery 医学-医药化学

CiteScore

1.80

自引率

10.00%

发文量

245

审稿时长

3 months

期刊介绍： Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.