Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives as potential antitumor candidate.

A novel class of tetrahydroisoquinoline derivatives was designed and synthesized as antitumor agents and evaluated for their in vitro and in vivo biological activities. The antiproliferative activities of all the target compounds on HUVEC, MCF-7, and HT-29 were evaluated. Compared with colchicine (1.04 × 10-2  μm), 17d and 17e exhibited outstanding activity on MCF-7 with IC50 values 0.26 × 10-2  μm and 0.89 × 10-3 μm in cell cytotoxicity assay. The tubulin polymerization assay demonstrated that 17d and 17e exhibited better inhibition rate. In the MCF-7-xenograft mouse model that was treated with 17d and 17e by intraperitoneal injection, the tumor weight was decreased at same rate with tamoxifen, and relative tumor proliferation rates were 59.48% and 41.33%, while tamoxifen was 45.08% with a daily dose of 20 mg/kg, which were demonstrated potent in vivo efficacy.