22. Synthesis and Biological Investigation of Δ12-Prostaglandin J3 (Δ12-PGJ3) Analogues and Related Compounds

K.C. Nicolaou, K.K. Pulukuri, S. Rigol, P. Heretsch, R. Yu, C.I. Grove, C.R.H. Hale, A.E. Marrouni, V. Fetz, M. Brönstrup, M. Aujay, J. Sandoval, J. Gavrilyuk— 2016

A series of Δ12-prostaglandin J3 (Δ12-PGJ3) 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.

Title22. Synthesis and Biological Investigation of Δ12-Prostaglandin J3 (Δ12-PGJ3) Analogues and Related Compounds
AuthorK.C. Nicolaou, K.K. Pulukuri, S. Rigol, P. Heretsch, R. Yu, C.I. Grove, C.R.H. Hale, A.E. Marrouni, V. Fetz, M. Brönstrup, M. Aujay, J. Sandoval, J. Gavrilyuk
Date2016
IdentifierDOI: 10.1021/jacs.6b02075
Source(s)
CitationJ. Am. Chem. Soc. 2016, 138, 6550-6560