Antitumor agents. Part 186: Synthesis and biological evaluation of demethylcolchiceinamide analogues as cytotoxic DNA topoisomerase II inhibitors Original Research Article

Demethylation of colchiceinamide (2) and its analogues (3–10) afforded a novel class of mammalian DNA topoisomerase II inhibitors (2a–10a) without displaying tubulin inhibitory activity. All target compounds inhibited the catalytic activity of topoisomerase II at drug concentrations at 100 μM. An in vitro cytotoxicity assay indicated that compounds 3a and 8a were strong and tissue-selective cytotoxic agents against the MCF-7 breast cancer cell line (IC50=0.36 and 0.48 μg/mL, respectively) and the CAKI-1 renal cancer cell line (IC50=0.72 and 0.96 μg/mL, respectively).