Asymmetric synthesis of antimitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells.
The (S,S)-enantiomer of combretadioxolane (3), designed as a chirally preorganized derivative of combretastatin A-4, exhibited quite strong tubulin polymerization-inhibitory activity (IC50: 4-6 microM). (S,S)-3 is 20 times more potent than vincristine as an in vitro growth inhibitor (in terms of GI50) of the multi-drug-resistant (MDR) cell line PC-12, which produces P-glycoprotein.
Shirai
R
R
Institute of Molecular and Cellular Biosciences (IMCB), University of Tokyo, Japan.
Takayama
H
H
Nishikawa
A
A
Koiso
Y
Y
Hashimoto
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D016716:PC12 Cells; D051381:Rats
D000970:Antineoplastic Agents; D004148:Dioxolanes; C116799:combretadioxolane