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- Title
Tricyclic Guanidine Alkaloids from the Marine Sponge Acanthella cavernosa that Stabilize the Tumor Suppressor PDCD4.
- Authors
Grkovic, Tanja; Blees, Johanna S.; Bayer, Magdalena M.; Colburn, Nancy H.; Thomas, Cheryl L.; Henrich, Curtis J.; Peach, Megan L.; McMahon, James B.; Schmid, Tobias; Gustafson, Kirk R.
- 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.
- Subjects
MARINE natural products; ALKALOIDS; THERAPEUTIC use of alkaloids; CANCER treatment; SPONGES (Invertebrates); TUMOR suppressor proteins; THERAPEUTICS
- Publication
Marine Drugs, 2014, Vol 12, Issue 8, p4593
- ISSN
1660-3397
- Publication type
Article
- DOI
10.3390/md12084593