甲氧基查尔酮类化合物的合成、体外抗宫颈癌活性及其与MDM2分子对接研究  

Synthesis of Methoxychalcones,Anti-cervical Cancer Activity In Vitro and Their Molecular Docking with MDM2

作　　者：廖波儿 郭伟[2] 木合布力·阿布力孜[2] LIAO Boer;GUO Wei;MOURBOUL Ablise(Central Laboratory,Xinjiang Medical University,Urumqi 830011,China;College of Pharmacy,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学中心实验室,新疆乌鲁木齐830011 [2]新疆医科大学药学院,新疆乌鲁木齐830011

出　　处：《合成化学》2025年第1期30-36,共7页Chinese Journal of Synthetic Chemistry

基　　金：新疆维吾尔自治区自然科学基金青年科学基金项目(2022D01C210)。

摘　　要：通过Claisen-Schmidt缩合反应原理,合成出4个甲氧基查尔酮类化合物,其结构均经^(1)H NMR、^(13)C NMR确证。以宫颈癌He La和Si Ha细胞作为受试细胞,测定目标化合物对细胞抑制作用及诱导凋亡作用,并通过分子对接技术研究化合物3,4,5-三甲氧基-2′,4′-二甲氧基查尔酮(3d)与MDM2蛋白构效关系。研究结果表明:4个甲氧查尔酮化合物均对宫颈癌He La和Si Ha细胞展现出较好的抑制活性,其中化合物3d对宫颈癌He La和Si Ha细胞抑制活性最高,作用24 h,IC_(50)为26.39μmol/L。在凋亡实验中,化合物3d显著诱导细胞凋亡,作用48 h,细胞凋亡率达到77%。分子对接结果显示:化合物3d与MDM2靶标蛋白的结合自由能为-6.2 kcal/mol,此结果表明;化合物3d与MDM2蛋白具有较高的结合性。Four methoxychalcone compounds were synthesized by Claisen-Schmidt condensation reaction principle,and their structures were confirmed by^(1)H NMR and^(13)C NMR.Cervical cancer HeLa and SiHa cells were used as test cells to determine the inhibitory and apoptosis-inducing effects of target compounds,and the structure-activity relationship between 3,4,5-trimethoxy-2',4'-dimethoxy-chalcone(3d)and MDM2 protein was studied by molecular docking technology.The results showed that all the four meoxychalcone compounds showed good inhibitory activity on HeLa and SiHa cells of cervical cancer,among which compound 3d had the highest inhibitory activity on HeLa and SiHa cells of cervical cancer,with an IC_(50)of 9.45μg/mL for 24 h.In the apoptosis experiment,compound 3d significantly induced apoptosis,and the apoptosis rate reached 77%after 48 h.The molecular docking results showed that the binding free energy of compound 3d to MDM2 target protein was-6.2 kcal/mol,which indicated that compound 3d had high binding ability to MDM2 protein.

关 键 词：甲氧基查尔酮 宫颈癌 合成 分子对接 MDM2蛋白 

分 类 号：R914.5[医药卫生—药物化学]