Synthesis and biological activity of A-nor-paclitaxel analogues.
A number of paclitaxel analogues with a 5-membered A-ring (A-nor-paclitaxels, or (15-->1)-abeo-paclitaxels) have been prepared in order to determine whether analogues of this class might have improved bioactivity as compared with paclitaxel. Most of the compounds synthesized were less active than paclitaxel, but one analogue was equivalent to paclitaxel in a tubulin-assembly assay, and another analogue was more cytotoxic than paclitaxel in two different cell lines of the NCI screen.
Chordia
M D
MD
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg 24061-0212, USA.
Kingston
D G
DG
Hamel
E
E
Lin
C M
CM
Long
B H
BH
Fairchild
C A
CA
Johnston
K A
KA
Rose
W C
WC
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel