Antitumor agents. Part 236: Synthesis of water-soluble colchicine derivatives.
Basic Information
ID: ALA1145225
Journal: Bioorg Med Chem Lett
Title: Antitumor agents. Part 236: Synthesis of water-soluble colchicine derivatives.
Authors: Nakagawa-Goto K, Chen CX, Hamel E, Wu CC, Bastow KF, Brossi A, Lee KH.
Abstract: Water-soluble colchicine derivatives were synthesized from 2-demethylcolchicine and 2-demethylthiocolchicine and evaluated in vitro against human tumor cell replication and for inhibition of tubulin polymerization. The glycinate esters (4, 5) and their tartaric acid salts (4a, 5a) showed potent cytotoxic activity in three different tumor cell lines with IC(50) values ranging from 0.02 to 0.88 microg/mL. The thiocolchicine analogs (5, 5a) were more potent than the colchicine analogs (4, 4a) in the tubulin polymerization assay. In particular, the water-soluble salt 5a merits preclinical development as an antitumor agent.
CiteXplore: 15582446
DOI: 10.1016/j.bmcl.2004.07.098
Patent ID: ┄