Tricyclic guanidine alkaloids from the marine sponge Acanthella cavernosa that stabilize the tumor suppressor PDCD4.

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.

• Authors: Tanja Grkovic, Johanna S Blees, Magdalena M Bayer, Nancy H Colburn, Cheryl L Thomas, Curtis J Henrich, Megan L Peach, James B McMahon, Tobias Schmid, Kirk R Gustafson
• Journal: Marine drugs (Mar Drugs) Vol. 12 Issue 8 Pg. 4593-601 (Aug 21 2014) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 25196934 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Apoptosis Regulatory Proteins
• PDCD4 protein, human
• RNA-Binding Proteins
• Saponins
• Tumor Suppressor Proteins
• mirabilin
• Oleanolic Acid
• Guanidine

Topics

• Alkaloids (chemistry, pharmacology)
• Animals
• Apoptosis Regulatory Proteins (metabolism)
• Guanidine (chemistry, pharmacology)
• HEK293 Cells
• Humans
• Oleanolic Acid (analogs & derivatives, chemistry)
• Porifera (chemistry)
• RNA-Binding Proteins (metabolism)
• Saponins (chemistry)
• Tumor Suppressor Proteins (metabolism)