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Mar Drugs. 2014 Aug 21;12(8):4593-601. doi: 10.3390/md12084593.

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

Author information

1
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. t.grkovic@griffith.edu.au.
2
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. M_Bajer@gmx.de.
3
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. M_Bajer@gmx.de.
4
Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. colburna@mail.nih.gov.
5
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. cltterry@mail.nih.gov.
6
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. henrichcj@mail.nih.gov.
7
Basic Science Program, Leidos Biomedical Research, Inc., Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. mpeach@helix.nih.gov.
8
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. mcmahoja@mail.nih.gov.
9
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. gustafki@mail.nih.gov.

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.

PMID:
25196934
PMCID:
PMC4145332
DOI:
10.3390/md12084593
[Indexed for MEDLINE]
Free PMC Article

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