Synthesis and cytotoxicity screening of derivatives of the simplified ecteinascidin pentacyclic skeleton as anticancer agents

A series of new ecteinascidin pentacyclic-derived compounds bearing aryl carboxylic amide side chains at C-22 have been designed and synthesized. The cytotoxicity evaluation confirmed their potent antitumor activity by use of eight different cell lines. Studies on the structure-activity relationship of them showed that the chemical structure of C-22 pendants have great effects on the tumor-killing activity. Notably, Compounds 6, 7 and 8 with benzo[b]thiophene-2-carboxamide pendants exhibited excellent broad-spectrum antitumor activity with the low IC50 values of 10−7 M.