Synthesis and interactions of 7-deoxy-, 10-deacetoxy, and 10-deacetoxy-7-deoxypaclitaxel with NCI/ADR-RES cancer cells and bovine brain microvessel endothelial cells.
7-Deoxypaclitaxel, 10-deacetoxypaclitaxel and 10-deacetoxy-7-deoxypaclitaxel were prepared and evaluated for their ability to promote assembly of tubulin into microtubules, their cytotoxicity against NCI/ADR-RES cells and for their interactions with P-glycoprotein in bovine brain microvessel endothelial cells. The three compounds were essentially equivalent to paclitaxel in cytotoxicity against NCI/ADR-RES cells. They also appeared to interact with P-glycoprotein in the endothelial cells with the two 10-deacetoxy compounds having less interaction than paclitaxel and 7-deoxypaclitaxel.
Ge
Haibo
H
Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA.
Vasandani
Veena
V
Huff
Jacquelyn K
JK
Audus
Kenneth L
KL
Himes
Richard H
RH
Seelig
Anna
A
Georg
Gunda I
GI
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008968:Molecular Conformation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C508212:10-deacetoxy-7-deoxypaclitaxel; C402708:10-deacetoxypaclitaxel; C508211:7-deoxypaclitaxel; D043823:Taxoids; D017239:Paclitaxel