Synthesis and bioactivity of 2,4-diacyl analogues of paclitaxel.
The 2,4-diacyl paclitaxel analogues 8a-8r were prepared from paclitaxel by acylation of 4-deacetyl-2-debenzoylpaclitaxel 1,2-carbonate (3) followed either by hydrolysis of the carbonate and acylation or by direct treatment of the carbonate with an aryllithium. Some of the resulting derivatives showed significantly improved tubulin assembly activity and cytotoxicity as compared with paclitaxel; in some cases this improvement was especially significant for paclitaxel-resistant cell lines.
Chordia
M D
MD
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0212, USA.
Yuan
H
H
Jagtap
P G
PG
Kadow
J F
JF
Long
B H
BH
Fairchild
C R
CR
Johnston
K A
KA
Kingston
D G
DG
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D002470:Cell Survival; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D008869:Microtubule-Associated Proteins; D017239:Paclitaxel