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MDPI, Marine Drugs, 8(12), p. 4593-4601, 2014

DOI: 10.3390/md12084593

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Tricyclic Guanidine Alkaloids from the Marine Sponge Acanthella cavernosa that Stabilize the Tumor Suppressor PDCD4

Journal article published in 2014 by Tanja Grkovic, Johanna S. Blees, Magdalena M. Bayer, Nancy H. Colburn, Cheryl L. Thomas, Curtis J. Henrich, Megan L. Peach ORCID, James B. McMahon, Tobias Schmid, Kirk R. Gustafson
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.