摘要
为了研究新型VEGFR-2抑制剂的合成方法及抗肿瘤活性,合成了9个含喹唑啉结构的VEGFR-2抑制剂,以MTT法测试了目标化合物对人结肠癌HCT-116和HT-29 2个细胞株的抑制活性,结果显示化合物A03、A05、A06、A07和A08比阳性对照索拉非尼的活性更好(IC_(50)<10μmol/L).为了阐明目标化合物和VEGFR-2的作用机制,分别将sorafenib和化合物A03与VEGFR-2(PDB:2OH4)的DFG-out构象进行了分子对接,结果表明该系列化合物可能作为Ⅱ型激酶抑制剂发挥抗肿瘤作用.
In order to study the synthesis and antitumor activity of novel VEGFtl-2 inhibitors, nine V EGFt/-2 in- hibitors containing quinazoline are synthesized. The inhibitory activity of target compounds on HCT-116 and HT-29 cells is tested by MTT assay. The results show that compounds A03, A05, A06, A07 and A08 have better activity （ IC50 〈 10 μmol/L） than positive control sorafenib. In order to elucidate the mechanism of interaction of the targel compound and VEGFR-2, sorafenib and A03 are respectively docked into the DFG-out conformation of VEGFR-2 （PDB ： 2OH4）. The results show that the series of compounds may as type Ⅱ kinase inhibitors to play anti-tumor effect.
出处
《烟台大学学报（自然科学与工程版）》
CAS
2018年第1期19-26,共8页
Journal of Yantai University(Natural Science and Engineering Edition)
基金
国家自然科学基金资助项目(81202038)
