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

International Journal of Molecular Sciences

Lutz F. Tietze¹  Olaf Panknin²  Birgit Krewer²  Felix Major² 

[1] id="af1-ijms-09-00821">Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077 Göttingen, Germa

关键词: antibiotics;    antitumor agents;    pentagastrin;    prodrug;    prodrug monotherapy;   

DOI  :  10.3390/ijms9050821

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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