Design, Synthesis And Screening Of The Compounds With Angiogenesis Activity

Tumorgenesis and development were caused by multiple reasons. In the past, the design of anticancer drugs was based on inhibiting the growth of tumor cells, and while this kind of drugs have many drawbacks in clinic, such as toxic side effect and drug-resistance. The recent achievement of clinical and basic medicine research confirmed that tumorgenesis,growing and metastasis were depended on angiogenesis,in addition,the rate that angiogenesis formed in tumor was faster than that of the normal tissues by 50-200 times, moreover the angiogenesis in adult people has been ceased. So inhibiting angiogenesis became a new target for anticancer drugs design.Angiogenesis was the rusult of the interaction betwin tumor cells, endothelial cells and extracellar matrix etc. Angiogenesis factors,such as VEGF(vascular endothelial growth factor) , bFGF(basic fibroblast growth factor) played the key roles in angiogenesis, so inhibiting the biological function of VEGFs or bFGFs can block angiogenesis. In this study, We designed and synthesized 43 compounds based on SD-structure of VEGFR,and screened then,in vivo or in vitro. 22 compounds can inhibit the growth of blood vessel endothelic cells,which was induced by bFGF(basic fibroblast growth factor) or VEGF. Among of them, 17compounds showed more potential than Su5416(Positive drug) in inhibiting angiogenesis which was induced by bFGF; 15 compounds showed more potential than Su5416(Positive drug) in inhibiting angiogenesis which was induced by VEGF; and 11 compounds showed more potential than Su5416(Positive drug) in inhibiting angiogenesis on two kinds of model which was induced by VEGF or bFGF. On CAM assay, 8 compounds can inhibit angiogenesis of CAM, among of them, 6 compounds showed more potent activity than that of Su5416.the inhibit rate was from 20.5% to 72.8%. On animal assay, One compound (No. 3) showed good effect on SI 80 tumor, the inhibiting rate was 53.7%,We also studied the activity of these compounds inducing apoptosis.The result indicated these compounds can induce apoptosis of tumor cells.