Bioactive Sesterterpenoids from a Korean Sponge <i>Monanchora</i> sp.

Chemical investigation of a Korean marine sponge, <i>Monanchora</i> sp., yielded nine new sesterterpenoids (<b>1</b>–<b>9</b>) along with phorbaketals A–C (<b>10</b>–<b>12</b>). The planar structures were established on the basis of NMR and MS analysis, and the absolute configurations of <b>1</b>–<b>9</b> were defined using the modified Mosher’s method and CD spectroscopic data analysis. Compounds <b>1</b>–<b>8</b>, designated as phorbaketals D–K, possess a spiroketal-modified benzopyran moiety such as phorbaketal A, and their structural variations are due to oxidation and/or reduction of the tricyclic core or the side chain. Compound <b>9</b>, designated as phorbin A, has a monocyclic structure and is proposed to be a possible biogenetic precursor of the phorbaketals. Compounds <b>1</b>–<b>9</b> were evaluated for cytotoxicity against four human cancer cell lines (A498, ACHN, MIA-paca, and PANC-1), and a few of them were found to exhibit cytotoxic activity

Phosphoiodyns A and B, Unique Phosphorus-Containing Iodinated Polyacetylenes from a Korean Sponge <i>Placospongia</i> sp.

Two unprecedented phosphorus-containing iodinated polyacetylenes, phosphoiodyns A and B (<b>1</b>–<b>2</b>), were isolated from a Korean marine sponge <i>Placospongia</i> sp. Their structures were elucidated by spectroscopic data analysis. Phosphoiodyn A exhibited potent agonistic activity on human peroxisome proliferator-activated receptor delta (hPPARδ) with an EC₅₀ of 23.7 nM

Identification of Antiangiogenic Potential and Cellular Mechanisms of Napyradiomycin A1 Isolated from the Marine-Derived <i>Streptomyces</i> sp. YP127

Angiogenesis is the process of new blood vessel formation. Excessive angiogenesis is a critical factor in the progression of cancer, macular degeneration, and other chronic inflammatory diseases. When investigating the effects of crude extracts of cultured marine microorganisms, an extract of the cultured <i>Streptomyces</i> sp. YP127 strain was found to inhibit human umbilical vein endothelial cell (HUVEC) tube formation. Bioassay-guided fractionation and spectroscopic data analyses led to the identification of napyradiomycin A1 (<b>1</b>) as an antiangiogenic component of the extract. Compound <b>1</b> inhibited HUVEC tube formation in a concentration-dependent manner. It inhibited endothelial cell proliferation but did not affect human dermal fibroblast proliferation. Compound <b>1</b> also suppressed migration and invasion of vascular endothelial cells. In addition, compound <b>1</b> suppressed vascular endothelial cadherin expression and increased the permeability of the endothelial cell membrane. These results suggested that compound <b>1</b> modulates cell permeability and inhibits the angiogenesis of endothelial cells

Acredinones A and B, Voltage-Dependent Potassium Channel Inhibitors from the Sponge-Derived Fungus <i>Acremonium</i> sp. F9A015

Two new benzophenones, acredinones A (<b>1</b>) and B (<b>2</b>), were isolated from a marine-sponge-associated <i>Acremonium</i> sp. fungus. Their chemical structures were elucidated on the interpretation of spectroscopic data. The structure of <b>1</b> was confirmed by palladium-catalyzed hydrogenation, followed by spectroscopic data analysis. Acredinones A (<b>1</b>) and B (<b>2</b>) inhibited the outward K⁺ currents of the insulin secreting cell line INS-1 with IC₅₀ values of 0.59 and 1.0 μM, respectively

Acredinones A and B, Voltage-Dependent Potassium Channel Inhibitors from the Sponge-Derived Fungus <i>Acremonium</i> sp. F9A015

Two new benzophenones, acredinones A (<b>1</b>) and B (<b>2</b>), were isolated from a marine-sponge-associated <i>Acremonium</i> sp. fungus. Their chemical structures were elucidated on the interpretation of spectroscopic data. The structure of <b>1</b> was confirmed by palladium-catalyzed hydrogenation, followed by spectroscopic data analysis. Acredinones A (<b>1</b>) and B (<b>2</b>) inhibited the outward K⁺ currents of the insulin secreting cell line INS-1 with IC₅₀ values of 0.59 and 1.0 μM, respectively

Insights of a Lead Optimization Study and Biological Evaluation of Novel 4‑Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists

We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERRγ but also exhibited enhanced pharmacokinetic profile compared with <b>3</b> (GSK5182). <b>6g</b> and <b>10b</b> had comparable potency to <b>3</b> and were far more selective for ERRγ over the ERRα, -β, and ERα. The in vivo pharmacokinetic profiles of <b>6g</b> and <b>10b</b> were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in <b>6g</b>- or <b>10b</b>-treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, <b>6g</b> and <b>10b</b> possess advantageous druglike properties and can be used to potentially treat various ERRγ-related disorders