Synthesis and Biological Investigation of Delta(12)-Prostaglandin J3 (Delta(12)-PGJ(3)) Analogues and Related Compounds

authored by

K. C. Nicolaou, Kiran Kumar Pulukuri, Stephan Rigol, Philipp Heretsch, Ruocheng Yu, Charles I. Grove, Christopher R. H. Hale, Abdelatif ElMarrouni, Verena Fetz, Mark Broenstrup, Monette Aujay, Joseph Sandoval, Julia Gavrilyuk

Abstract

A series of δ

¹²-prostaglandin J

₃ (δ

¹²-PGJ

₃) analogues and derivatives were synthesized employing an array of synthetic strategies developed specifically to render them readily available for biological investigations. The synthesized compounds were evaluated for their cytotoxicity against a number of cancer cell lines, revealing nanomolar potencies for a number of them against certain cancer cell lines. Four analogues (2, 11, 21, and 27) demonstrated inhibition of nuclear export through a covalent addition at Cys528 of the export receptor Crm1. One of these compounds (i.e., 11) is currently under evaluation as a potential drug candidate for the treatment of certain types of cancer. These studies culminated in useful and path-pointing structure-activity relationships (SARs) that provide guidance for further improvements in the biological/pharmacological profiles of compounds within this class.

External Organisation(s)

Rice University
Helmholtz Centre for Infection Research (HZI)

Type

Article

Journal

Journal of the American Chemical Society

Volume

138

Pages

6550-6560

No. of pages

ISSN

0002-7863

Publication date

25.05.2016

Publication status

Published

Peer reviewed

Yes

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1021/jacs.6b02075 (Access: Closed)