新型VEGFR2-HDAC6抑制剂设计、合成和抗癌活性评价  

Designs,Synthesis,and Anti-cancer Activity Evaluations of Novel VEGFR2-HDAC6 Inhibitors

作　　者：喻明军 陈雨涵 杨友亮 闫威 曹刚刚 YU Mingjun;CHEN Yuhan;YANFG Youliang;YAN Wei;CAO Ganggang(College of Traditional Chinese Medicine,Bozhou University,Bozhou Anhui 236800;Anhui Gujing Health Technology Co.,Ltd.,Bozhou Anhui 236821)

机构地区：[1]亳州学院中药学院,安徽亳州236800 [2]安徽古井健康科技有限公司,安徽亳州236821

出　　处：《兴义民族师范学院学报》2025年第1期107-113,共7页Journal of Minzu Normal University of Xingyi

基　　金：安徽省教育厅重点研究项目“微管蛋白-HDAC6双重抑制剂的研发及抗癌活性研究”(项目编号:2022AH052409);2024年安徽省高校理工科教师赴企业挂职实践计划项目(项目编号:2024jsqygz135);亳州学院重点研究项目“含查尔酮结构HDAC6抑制剂的合成及抗癌活性研究”(项目编号:BYZ2021BO1)。

摘　　要：通过分子杂合原理,设计、合成了5个含查尔酮片段的HDAC6-VEGFR-2双重抑制剂,并评价了其抗癌活性。化合物4a—4e对K562和Siha细胞具有较强的细胞毒性,其中化合物4b和4e的活性强于其余化合物和阳性对照Sorafenib和SAHA,其IC50值在0.67—1.04μM之间。化合物4b和4e在体外对HDAC6和VEGFR-2蛋白都具有较强的亲和性,其IC_(50)值在197—935nM之间,分子对接结果也证实4b和4e与HDAC6和VEGFR-2蛋白都具有较强的亲和性。Five HDAC6-VEGFR-2 dual inhibitors containing chalcone fragments were designed and synthesized based on the principle of molecular hybridization,and their anti-cancer activities were evaluated.Compounds 4a-4e had strong cytotoxicity against K562 and Siha cells,with compounds 4b and 4e exhibiting stronger activity than the other compounds and positive controls Sorafenib and SAHA,with IC_(50) values ranging from 0.67 to 1.04μM.Compounds 4b and 4e exhibit strong affinity for both HDAC6 and VEGFR-2 proteins in vitro,with IC50 values ranging from 197-935nM.Molecular docking results also confirm that compounds 4b and 4e have strong affinity for both HDAC6 and VEGFR-2 proteins.

关 键 词：查尔酮 VEGFR-2抑制剂 HDAC6抑制剂 抗癌活性 

分 类 号：R979.1[医药卫生—药品]