title: Antitumor agents. Part 236: Synthesis of water-soluble colchicine derivatives.
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.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakagawa-Goto
authors.forename: Cyril X
authors.initials: CX
authors.lastname: Chen
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Wu
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Arnold
authors.initials: A
authors.lastname: Brossi
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D014867:Water; D003078:Colchicine