Synthesis and biological evaluation of prodrugs based on the natural antibiotic duocarmycin for use in ADEPT and PMT.

Authors :: Tietze LF
Schmuck K
Schuster HJ
Müller M
Schuberth I
Source :: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2011 Feb 07; Vol. 17 (6), pp. 1922-9. Date of Electronic Publication: 2011 Jan 07.
Publication Year :: 2011
Abstract: Chemotherapy of malign tumors is usually associated with serious side effects as common anticancer drugs lack selectivity. An approach to deal with this problem is the antibody-directed enzyme prodrug therapy (ADEPT) and the prodrug monotherapy (PMT). Herein, the synthesis and biological evaluation of new glycosidic prodrugs suitable for both concepts are described. All prodrugs but one are stable in human serum and show QIC(50) values (IC(50) of prodrug/IC(50) of prodrug in the presence of the appropriate glycohydrolase) of up to 6500. This is the best value found so far for compounds interacting with DNA.<br /> (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Subjects :: Antibodies therapeutic use
Drug Screening Assays, Antitumor
Duocarmycins
Glucuronidase metabolism
Humans
Inhibitory Concentration 50
Molecular Structure
Pyrroles chemical synthesis
Pyrroles chemistry
Pyrroles therapeutic use
DNA metabolism
Drug Design
Indoles chemical synthesis
Indoles chemistry
Indoles therapeutic use
Prodrugs chemical synthesis
Prodrugs chemistry
Prodrugs therapeutic use

Full Text Access

Tools