Synthesis and bioactivity of a side chain bridged paclitaxel: A test of the T-Taxol conformation.
A knowledge of the bioactive tubulin-binding conformation of paclitaxel (Taxol()) is crucial to a full understanding of the bioactivity of this important anticancer drug, and potentially also to the design of simplified analogs. The bioactive conformation has been shown to be best approximated by the T-Taxol conformation. As a further test of this conclusion, the paclitaxel analog 4 was designed as a compound which has all the chemical functionality necessary for activity, but which cannot adopt the T-Taxol conformation. The synthesis and bioassay of 4 confirmed its lack of activity, and thus provided further support for the T-Taxol conformation as the bioactive tubulin-binding conformation.
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, 24061, USA.
Mathis
M
Hodge
Qiao-Hong
QH
Chen
Susan
S
Bane
Shubhada
S
Sharma
Maura
M
Loew
Abhijit
A
Banerjee
Ana A
AA
Alcaraz
James P
JP
Snyder
David G I
DG
Kingston
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D002219:Carbamates; D014404:Tubulin; D017239:Paclitaxel