Synthesis and biological studies of different duocarmycin based glycosidic prodrugs for their use in the antibody-directed enzyme prodrug therapy.
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.
Tietze
Lutz F
LF
Institute of Organic and Biomolecular Chemistry Georg-August-University Gottingen, Tammannstrasse 2, D-37077 Gottingen, Germany. ltietze@gwdg.de
Schuster
Heiko J
HJ
Krewer
Birgit
B
Schuberth
Ingrid
I
D000906:Antibodies / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D000080890:Duocarmycins; D006027:Glycosides / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D001616:beta-Galactosidase / Q000627:therapeutic use*
D000906:Antibodies; D000080890:Duocarmycins; D006027:Glycosides; D007211:Indoles; D011355:Prodrugs; D011758:Pyrroles; C066098:duocarmycin SA; D001616:beta-Galactosidase