Synthesis and biological evaluation of a novel pentagastrin-toxin conjugate designed for a targeted prodrug mono-therapy of cancer.

Abstract

A novel carbamate prodrug 2 containing a pentagastrin moiety was synthesized. 2 was designed as a detoxified analogue of the highly cytotoxic natural antibiotic duocarmycin SA (1) for the use in a targeted prodrug monotherapy of cancers expressing cholecystokinin (CCK-B)/gastrin receptors. The synthesis of prodrug 2 was performed using a palladium-catalyzed carbonylation of bromide 6, followed by a radical cyclisation to give the pharmacophoric unit 10, coupling of 10 to the DNA-binding subunit 15 and transformation of the resulting seco-drug 3b into the carbamate 2 via addition of a pentagastrin moiety.

• Authors: Lutz F Tietze, Olaf Panknin, Birgit Krewer, Felix Major, Ingrid Schuberth
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 9 Issue 5 Pg. 821-837 (May 2008) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 19325786 (Publication Type: Journal Article)