Synthesis and Biological Evaluation of a Novel Pentagastrin- Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer

doi:10.3390/ijms9050821

This article is

freely available
re-usable

Int. J. Mol. Sci. 2008, 9(5), 821-837; doi:10.3390/ijms9050821

Article

Synthesis and Biological Evaluation of a Novel Pentagastrin- Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer

Lutz F. Tietze * , Olaf Panknin, Birgit Krewer, Felix Major and Ingrid Schuberth

Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany

^* Author to whom correspondence should be addressed.

Received: 25 April 2008; in revised form: 15 May 2008 / Accepted: 16 May 2008 / Published: 20 May 2008

(This article belongs to the Special Issue Natural Compounds for Cancer Treatment and Prevention)

Download PDF Full-Text [273 KB, uploaded 2 October 2008 12:05 CET]

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.

Keywords: antibiotics; antitumor agents; pentagastrin; prodrug; prodrug monotherapy

Article Statistics

Click here to load and display the download statistics.

Cite This Article

MDPI and ACS Style

Tietze, L.F.; Panknin, O.; Krewer, B.; Major, F.; Schuberth, I. Synthesis and Biological Evaluation of a Novel Pentagastrin- Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer. Int. J. Mol. Sci. 2008, 9, 821-837.

AMA Style

Tietze L.F., Panknin O., Krewer B., Major F., Schuberth I. Synthesis and Biological Evaluation of a Novel Pentagastrin- Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer. International Journal of Molecular Sciences. 2008; 9(5):821-837.

Chicago/Turabian Style

Tietze, Lutz F.; Panknin, Olaf; Krewer, Birgit; Major, Felix; Schuberth, Ingrid. 2008. "Synthesis and Biological Evaluation of a Novel Pentagastrin- Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer." Int. J. Mol. Sci. 9, no. 5: 821-837.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI Publishing, Basel, Switzerland RSS E-Mail Table of Contents Alert