Syntheses and biological activity of C-3'-difluoromethyl-taxoids.

Abstract

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.

• Authors: I Ojima, S Lin, J C Slater, T Wang, P Pera, R J Bernacki, C Ferlini, G Scambia
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 8 Issue 7 Pg. 1619-28 (Jul 2000) ISSN: 0968-0896 [Print] England
• PMID: 10976509 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• SB T-12843
• Taxoids
• Docetaxel
• Paclitaxel

Topics

• Antineoplastic Agents, Phytogenic (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• DNA Fragmentation (drug effects)
• Docetaxel
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Flow Cytometry
• Humans
• Inhibitory Concentration 50
• Paclitaxel (analogs & derivatives, chemistry, pharmacology)
• Structure-Activity Relationship
• Taxoids
• Tumor Cells, Cultured