Highly increased cellular accumulation of vincristine, a useful hydrophobic antitumor-drug, in multidrug-resistant solid cancer cells induced by a simply reduced taxinine.
Regio- and/or chemo-selective reductions of taxinine (1a), a taxane diterpenoid readily obtainable from the needles of a Japanese yew (Taxus cuspidata), at the 5-O-cinnamoyl and 4-exo-methylene moieties have been accomplished by the catalytic hydrogenation over Pd/C or Rh/C to obtain 5-O-phenylpropionylated taxinine A (1b), 5-O-cyclohexylpropionylated taxinine A (1c), and 5-O-phenylpropionylated 4,20-dihydrotaxinine A (2a) in almost quantitative yields, respectively. Among them, taxoid 1b was found to be highly effective in increasing the cellular accumulation of vincristine in the multidrug-resistant human ovarian cancer cells compared with the cases of verapamil and the previously reported taxoids.
Sako
M
M
Gifu Pharmaceutical University, Japan.
Suzuki
H
H
Yamamoto
N
N
Hirota
K
K
D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D043823:Taxoids; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000493:pharmacokinetics*
C403247:5-O-phenylpropionyloxytaxinine A; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D014750:Vincristine; D017239:Paclitaxel