基于喹唑啉酮基团的查尔酮衍生物的设计、合成与初步活性筛选  

Design,synthesis and preliminary evaluation of chalcone derivatives based on quinazolone scaffold

作　　者：单媛媛[1] 马瑛[1] 封卫毅[1] SHAN Yuanyuan;MA Ying;FENG Weiyi(Department of Pharmacy,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院药学部,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2020年第5期747-751,776,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81302641);陕西省自然科学基金资助(No.2018JM7071)。

摘　　要：目的基于受体酪氨酸激酶抑制剂的喹唑啉酮药效团,发现抗肿瘤活性的查尔酮衍生物。方法查尔酮骨架上引入喹唑啉酮片段,设计、合成了2类查尔酮衍生物。采用ADP-Glo TM方法评价对EGFR、KDR和FGFR13种肿瘤相关RTKs的抑制活性,采用MTT方法评价化合物的抗肿瘤活性。结果大部分化合物具有较好的RTKs抑制活性和抗肿瘤活性,部分化合物的活性接近吉非替尼。结论新型查尔酮衍生物具有潜在抗肿瘤活性,为抗肿瘤药物的发现奠定了基础。Objective To design and synthesize novel chalcone derivatives based on quinazolone scaffold of RTK inhibitors and develop novel anti-cancer agents through preliminary evaluation in vitro.Methods Two series of chalcone derivatives(QZO1-QZO14)were synthesized and their structures were confirmed.All the title compounds were evaluated for their enzymatic inhibition against EGFR,KDR and FGFR1by using ADP-Glo TM assays.The antiproliferative activities against MCF-7,A549 and K562 were identified by using MTT.Results Most of the title compounds exhibited potent multiple RTK inhibition and antiproliferative activities,which were comparable to those of the positive control.Conclusion Our studies provided the first generation of chalcone-based multi-target RTK inhibitors as anticancer agents.

关 键 词：喹唑啉酮 查尔酮衍生物 受体酪氨酸激酶 抗增殖活性 肿瘤细胞株 

分 类 号：R917[医药卫生—药物分析学]