Design, synthesis, and biological evaluation of simplified tetrahydroisoquinoline analogs

A series of tetrahydroisoquinoline derivatives were prepared and their antitumor activity was studied against several human carcinoma cell lines, including Ketr3, BEL-7402, BGC-823, KB, HCT-8, MCF-7, HeLa, A2780, A549, and HT-1080. Compound 20, an analog of phthalascidin 650, exhibited good broad-spectrum antitumor activity in vitro. However, compounds 19 and 21, in which the side chains at C-22 are simplified, showed no obvious antitumor activity, indicating that the C-22 side chain of this type of compound has a greater impact on its activity. The difference in the in vivo activity between compound 20 and phthalascidin 650 also shows a significant effect of the substituents on the skeleton structure on the in vivo activity. Since ecteinascidin 743 has been marketed as an anticancer drug, synthetic chemists have paid considerable efforts to its structural modifications. In this paper, a series of phthalascidin 650 analogs were synthesized and evaluated for their biological activity. The results of the antitumor activity tests in vitro and in vivo provide a new scientific basis for studying the structure-activity relationship of these derivatives.image