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芳香烯胺酮类化合物的合成与抗肿瘤活性分析

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随着人口增长和老龄化严重,全球癌症治疗负担也在同步增加,为获得具有更优性质的潜在抗肿瘤药物,设计、合成了 12个烯胺酮类化合物(3a～31).化合物结构通过1H NMR进行确证,接着采用Schrödingers Maestro软件将目标产物与抗肿瘤有关的8个靶蛋白进行分子对接预测其活性,并通过MTT(噻唑蓝)实验进行验证.对接结果通过Discovery Studio软件进行可视化分析,进一步明确其结合模式.结果表明:大多数化合物的产率良好至优,目标产物与8种蛋白均有不同程度的结合.目标化合物可通过Pi-Alkyl键、氢键和范德华力等多种分子间作用力与靶标蛋白活性位点附近的氨基酸残基结合,进而产生抗癌效应.其中,化合物3f与靶蛋白VEGFR2的对接效果最佳,普遍优于其他7个靶蛋白,具有较强的结合亲和力.此外,化合物3f对白血病细胞(K562)的抗增殖活性优于顺铂,化合物3b对宫颈癌细胞(Hela)的抗增殖活性优于顺铂.该研究可为基于靶点的抗肿瘤药物研发奠定一定的基础.
Synthesis and Antitumor Activity Analysis of Aryl Enaminone Compounds
As the global burden of cancer treatment is increasing simultaneously with population growth and severe aging,12 enaminones(3a～3l)were designed and synthesized to obtain potential antitu-mor drugs with superior properties.The structures of the compounds were confirmed by 1H NMR,fol-lowed by molecular docking of the target products with eight target proteins related to antitumor to pre-dict their activities using Schrödingers Maestro software,and verified by MTT(thiazolyl blue)assay.The docking results were visualized and analyzed by Discovery Studio software to further clarify the binding modes.The results showed that the yields of most compounds were good to excellent,and the target products were bound to all eight proteins to different degrees.The target compounds could bind to the amino acid residues near the active sites of the target proteins through various intermolecular forces,such as Pi-Alkyl bonding,hydrogen bonding and van der Waals force,and then produce anti-cancer effects.Among them,compound 3f had the best docking effect with the target protein VEG-FR2,which was generally superior to the other seven target proteins with strong binding affinity.In ad-dition,compound 3f showed better antiproliferative activity than cisplatin against leukemia cells(K562),and compound 3b showed better antiproliferative activity than cisplatin against cervical canc-er cells(Hela).This study may lay a certain foundation for the development of target-based antitumor drugs.

enaminonemolecular dockingantitumortarget proteinsynthesis

王滔、周英、董张超、石洋、潘博文

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贵州中医药大学药学院,贵州贵阳 550025

烯胺酮 分子对接 抗肿瘤 靶蛋白 合成

贵阳市科技计划项目贵州省基础研究计划项目(自然科学)贵州省基础研究计划项目(自然科学)贵州中医药管理局中医药与民族医药科学技术研究项目贵州省教育厅青年科技人才成长项目贵州省卫生健康委科学技术基金项目贵州省卫生健康委科学技术基金项目

[2024]2-37ZK[2023]404号ZK[2024]370号QZYY-2024-130黔教合KY字[2022]253号gzwkj2022-232gzwkj2022-467

2024

10.15952/j.cnki.cjsc.1005-1511.24072

合成化学
四川省化学化工学会　中国科学院成都有机化学研究所

合成化学

CSTPCD
影响因子：0.42
ISSN：1005-1511
年,卷(期)：2024.32(8)