Journal
MARINE DRUGS
Volume 12, Issue 8, Pages 4593-4601Publisher
MDPI AG
DOI: 10.3390/md12084593
Keywords
natural product; guanidine alkaloid; PDCD4; tumor suppressor
Categories
Funding
- NIH, National Cancer Institute, Center for Cancer Research
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- Deutsche Forschungsgemeinschaft (DFG) [GRK1172]
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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 mu g/mL and 2.8 mu g/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.
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