含喹唑啉结构的VEGFR-2抑制剂的合成、体外抗肿瘤活性与分子对接研究

摘要

In order to study the synthesis and antitumor activity of novel VEGFR-2 inhibitors,nine VEGFR-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 target 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 Ⅱkinase inhibitors to play anti-tumor effect.%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-292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(IC50<10 μmol/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.