Tricyclic Guanidine Alkaloids from the Marine Sponge Acanthella cavernosa that Stabilize the Tumor Suppressor PDCD4
نویسندگان
چکیده
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.
منابع مشابه
Formamido-Diterpenes from the South China Sea Sponge Acanthella cavernosa
Seven new formamido-diterpenes, cavernenes A-D (1-4), kalihinenes E and F (5-6), and kalihipyran C (7), together with five known compounds (8-12), were isolated from the South China Sea sponge Acanthella cavernosa. Structures were established using IR, HRESIMS, 1D and 2D NMR, and single X-ray diffraction techniques. The isolated compounds were assessed for their cytotoxicity against a small pan...
متن کاملGuanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro
Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge M...
متن کاملMarine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model
The marine environment constitutes an extraordinary resource for the discovery of new therapeutic agents. In the present manuscript we studied the effect of 3 different sponge derived guanidine alkaloids, crambescidine-816, -830, and -800. We show that these compounds strongly inhibit tumor cell proliferation by down-regulating cyclin-dependent kinases 2/6 and cyclins D/A expression while up-re...
متن کاملHow Environmental Factors Affect the Production of Guanidine Alkaloids by the Mediterranean Sponge Crambe crambe
Most marine sponges are known to produce a large array of low molecular-weight metabolites which have applications in the pharmaceutical industry. The production of so-called specialized metabolites may be closely related to environmental factors. In this context, assessing the contribution of factors like temperature, nutrients or light to the metabolomes of sponges provides relevant insights ...
متن کاملBatzella, Crambe and Monanchora: Highly Prolific Marine Sponge Genera Yielding Compounds with Potential Applications for Cancer and Other Therapeutic Areas
Pyrroloquinoline and guanidine-derived alkaloids present distinct groups of marine secondary metabolites with structural diversity that displayed potentialities in biological research. A considerable number of these molecular architectures had been recorded from marine sponges belonging to different marine genera, including Batzella, Crambe, Monanchora, Clathria, Ptilocaulis and New Caledonian ...
متن کامل