基于磺酰胺药效团的查尔酮衍生物的合成与活性筛选  

Synthesis and activity screening of chalcone derivatives based on sulfamide

作　　者：卢闻[1] 屈清慧[1] 刘婷婷[2] 马瑛[2] 单媛媛[2] LU Wen;QU Qinghui;LIU Tingting;MA Ying;SHAN Yuanyuan(School of Pharmacy,Xi′an Jiaotong University,Xi′an 710061,China;Department of Pharmacy,the First Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710061,China)

机构地区：[1]西安交通大学药学院,西安710061 [2]西安交通大学第一附属医院药学部,西安710061

出　　处：《西北药学杂志》2020年第5期710-715,共6页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81302641);陕西省自然科学基金项目(编号:2018JM7071);陕西省自然科学基础研究计划项目(编号:2020JM-023)。

摘　　要：目的消除查尔酮α,β-双键的不利影响,发现多靶标受体酪氨酸激酶(RTKs)抑制剂。方法查尔酮骨架上引入磺酰胺,设计并合成14个查尔酮衍生物(SFA1~SFA14)。分别采用酪氨酸激酶检测试剂盒(ADP-Glo TM)和四唑盐比色试验法(MTT)评价化合物对表皮生长因子受体(EGFR)、激酶插入区受体(KDR)和成纤维细胞生长因子受体1(FGFR1)以及乳腺癌细胞(MCF-7)、非小细胞肺癌细胞(A549)和白血病细胞(K562)的抑制活性。结果大部分化合物具有高效RTKs抑制活性和抗肿瘤活性,部分化合物活性接近阳性对照的水平。结论查尔酮磺酰胺衍生物具有潜在抗肿瘤活性。Objective To develop novel multi-target receptor tyrosine kinases(RTKs)inhibitors withoutα,β-unsaturated double bond.Methods 14 chalcone derivatives(SFA1-SFA 14)were designed and synthesized through incorporating of sulfamide into chalcone scaffold.All the compounds were evaluated for their enzymatic inhibition against epidermal growth factor receptor(EGFR),kinase insert domain receptor(KDR)and fibroblast growth factor receptor1(FGFR1)by using ADP-Glo TM assays.The anti-proliferative activity against MCF-7,A549 and K562 were identified by using MTT.Results Most of the title compounds exhibited potent multiple RTKs inhibition and anti-proliferative activities,which was comparable to that of the positive control.Conclusion Chalcone sulfonamide derivatives have potential antitumor activities.

关 键 词：磺酰胺 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：R914[医药卫生—药物化学]