Synthesis and preliminary biological evaluation of novel taspine derivatives as anticancer agents

Antiangiogenic therapy might represent a new promising anticancer therapeutic strategy. Taspine can significantly inhibit cell proliferation of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor-165, which is crucial for angiogenesis. In this study, a series of novel taspine derivatives were synthesized and screened for in vitro anticancer and antiangiogenesis activities. The majority of the derivatives demonstrated a moderate degree of cytotoxicity against human cancer cell lines. One of them (14) exhibited much better antiproliferative activity against CACO-2 (IC50 = 52.5 μM) and ECV304 (IC50 = 2.67 μM) cells than taspine did. Some of them were also effective in antiproliferative assays against HUVECs. The in silico estimate of solubility of title compounds were higher than that of taspine.

The compound 28 was built and docked into the active site of bFGFR-1 (PDB ID: 3C4F) using Sybyl 7.0. The docking result was showed by PyMOL.Figure optionsDownload as PowerPoint slide