Syntheses and Structure Activity Relationships of Taxoids Derived from14b-Hydroxy-10-deacetylbaccatin III
著者
和文:
Iwao Ojima,
John C. Slater,
Young Hoon Park,
Scott D. Kuduk,
TAKEUCHI CRAIG,
Rayomand H. Gimi,
Chung-Ming Sun,
Paula Pera,
Jean M. Veith,
Ralph J. Bernacki.
英文:
Iwao Ojima,
John C. Slater,
Young Hoon Park,
Scott D. Kuduk,
Craig Takeuchi,
Rayomand H. Gimi,
Chung-Ming Sun,
Paula Pera,
Jean M. Veith,
Ralph J. Bernacki.
A series of new taxoids derived from 14b-hydroxy-10-deacetylbaccatin III was synthesized by
means of the b-lactam synthon method. Most of the new taxoids thus synthesized possess
excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-
29), and breast (MCF-7) cancer cell lines, and several of these taxoids show subnanomolar
IC50 values which are severalfold to 1 order of magnitude better than those of paclitaxel and
docetaxel. Modifications at the 3'- and 3'-N-positions exert marked effects on the activity. For
the substituents at C-3', the cytotoxicity decreases in the order 2-furyl ~ 2-methyl-1-propenyl
> 2-methylpropyl > (E)-1-propenyl > n-propyl > phenyl >> 2,2-dimethylpropyl. For the 3'-N
substituents, the activity decreases in the order t-BuOCO > Ph > n-hexanoyl. A significant
increase in the cytotoxicity against the doxorubicin-resistant human breast cancer cell line
MCF7-R that expresses the multidrug resistance (MDR) phenotype is observed by the proper
modification of the substituent at C-10. The observed remarkable effects of the substituents
at C-10 on the activity against MCF7-R can be ascribed to the effective inhibition of the binding
of these new taxoids to P-glycoprotein that is responsible for MDR.
各種検索
サポート
ヘルプ