First enzymatically activated Taxotere prodrugs designed for ADEPT and PMT.
Described here are the syntheses and preliminary biological evaluations of the first two enzymatically activated prodrugs of docetaxel (Taxotere) reported to date. These prodrugs were designed as potential candidates for selective chemotherapy in ADEPT or PMT. They are constituted of a glucuronic acid moiety, a double spacer and the cytotoxic drug, differing only by the spacer substitution. The prodrugs were stable in a buffer, and the in vitro studies showed good detoxification and hydrolysis kinetics. As docetaxel was efficiently released in both cases, these compounds are very valuable candidates for further biological evaluations.
UMR176 CNRS/Institut Curie, Section Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Emmanuel
E
Bouvier
Sylvie
S
Thirot
Frédéric
F
Schmidt
Claude
C
Monneret
D000818:Animals; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D000077143:Docetaxel; D016503:Drug Delivery Systems; D004355:Drug Stability; D029968:Escherichia coli Proteins / Q000378:metabolism; D005965:Glucuronates / Q000737:chemistry; D005966:Glucuronidase / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism*; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry
D003432:Cross-Linking Reagents; D029968:Escherichia coli Proteins; D005965:Glucuronates; D011355:Prodrugs; D043823:Taxoids; D000077143:Docetaxel; D005966:Glucuronidase