Bridging converts a noncytotoxic nor-paclitaxel derivative to a cytotoxic analogue by constraining it to the T-Taxol conformation.
The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test of the T-Taxol conformational hypothesis. Although the unbridged A-nor-paclitaxel 3 is essentially noncytotoxic, the bridged analogue 4 is strongly cytotoxic. This result provides strong evidence for the T-Taxol conformation as the bioactive tubulin-binding conformation of paclitaxel.
Tang
Shoubin
S
Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Yang
Chao
C
Brodie
Peggy
P
Bane
Susan
S
Ravindra
Rudravajhala
R
Sharma
Shubhada
S
Jiang
Yi
Y
Snyder
James P
JP
Kingston
David G I
DG
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D008958:Models, Molecular; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D014404:Tubulin / Q000737:chemistry
D000970:Antineoplastic Agents; D014404:Tubulin; D017239:Paclitaxel