New Taxol (paclitaxel) prodrugs designed for ADEPT and PMT strategies in cancer chemotherapy.
Two new glucuronide paclitaxel prodrugs have been synthesized. Linked to the 2'-OH of the drug by a carbonate function, they include a self-immolative spacer bearing an arylnitro or arylamino group between the drug and the glucuronic acid residue. Both prodrugs were well detoxified and easily cleaved in the presence of beta-D-glucuronidase with fast removal of the spacer, releasing paclitaxel. The arylamino spacer-containing prodrug, more stable than the corresponding nitro analogue, was selected for further studies.
Alaoui
Abdessamad El
AE
UMR 176 CNRS/Institut Curie, Centre de Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Saha
Nabendu
N
Schmidt
Frédéric
F
Monneret
Claude
C
Florent
Jean-Claude
JC
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000201:enzymology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011355:Prodrugs; D005966:Glucuronidase; D017239:Paclitaxel