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Application of the ADEPT strategy to the MDR resistance in cancer chemotherapy
1Laboratoire de Pharmacognosie, URA CNRS 1310, Université Paris V, France.
Anti-Cancer Drug Design
|July 16, 1999
Abstract:
New prodrugs consisting of a beta-D-glucuronic acid linked to a MDR reversal agent (verapamil, quinine or dipyridamole) through a self-immolative spacer were synthesized. Four of them were selected for their reduced cytoxicity and beta-glucuronidase enzymatic efficient hydrolysis. Combined use of these prodrugs with a beta-D-glucuronyl-spacer-doxorubicin (HMR1826) according to an ADEPT strategy restored in vitro the sensibility of a MDR resistant strain.