Syntheses and biological activity of C-3'-difluoromethyl-taxoids.
A series of new taxoids bearing difluoromethyl group at the C-3' position and modifications at the C-10 and C-14 positions has been synthesized and their biological activities studied. The in vitro cytotoxicity assay results indicate that these newly developed taxoids exhibit comparable to several times better activity against drug-sensitive cell line LCC6-WT, and 40-70 times better activity against the corresponding drug-resistant cancer cell line LCC6-MDR as compared to that of paclitaxel. Apoptosis analysis has revealed the exceptional activity of SB-T-12843 (1e) in inducing apoptosis in both MDR-bearing and MDR-negative cancer cells.
Ojima
I
I
Department of Chemistry, State University of New York at Stony Brook, 11794, USA. iojima@notes.cc.sunysb.edu
Lin
S
S
Slater
J C
JC
Wang
T
T
Pera
P
P
Bernacki
R J
RJ
Ferlini
C
C
Scambia
G
G
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; C418206:SB T-12843; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel