Synthesis and Biological Studies of Different Duocarmycin Based Glycosidic Prodrugs for Their Use in the Antibody-Directed Enzyme Prodrug Therapy

ISSN
0022-2623
Date Issued
2009
Author(s)
Schuster, Heiko J.
Krewer, Birgit
Schuberth, Ingrid
DOI
10.1021/jm8009102
Abstract
The synthesis and biological evaluation of novel prodrugs for use in the antibody directed enzyme prodrug therapy (ADEPT) of cancer based on the cytotoxic antibiotic duocarmycin SA (1) are described. In this approach, we investigated the influence of the sugar moiety of the glycosidic prodrug on the QIC(50) values as well as on the stability and the water solubility. The best result was found for prodrug 22 containing an alpha-mannoside moiety with a QIC(50) value of 4500.