Dong Hwan Won

Anmindenols A and B, Inducible Nitric Oxide Synthase Inhibitors from a Marine-Derived Streptomyces sp.

Anmindenols A (1) and B (2), inhibitors of inducible nitric oxide synthase (iNOS), were isolated from a marine-derived bacterium Streptomyces sp. Their chemical structures were elucidated by interpreting various spectroscopic data, including IR, MS, and NMR. Anmindenols A and B are sesquiterpenoids possessing an indene moiety with five- and six-membered rings derived from isoprenyl units. The absolute configuration of C-4 in anmindenol B was determined by electronic circular dichroism (ECD) of a dimolybdenum complex. Anmindenols A (1) and B (2) inhibited nitric oxide production in stimulated RAW 264.7 macrophage cells with IC50 values of 23 and 19 μM, respectively.

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

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

Placotylene A, an Inhibitor of the Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclast Differentiation, from a Korean Sponge Placospongia sp.

A new inhibitor, placotylene A (1), of the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation, and a regioisomer of placotylene A, placotylene B (2), were isolated from a Korean marine sponge Placospongia sp. The chemical structures of placotylenes A and B were elucidated on the basis of 1D and 2D NMR, along with MS spectral analysis and revealed as an iodinated polyacetylene class of natural products. Placotylene A (1) displayed inhibitory activity against RANKL-induced osteoclast differentiation at 10 μM while placotylene B (2) did not show any significant activity up to 100 μM, respectively.

Monanchosterols A and B, Bioactive Bicyclo[4.3.1]steroids from a Korean Sponge Monanchora sp.

Chemical investigation of a Korean marine sponge, Monanchora sp., led to the isolation of three new steroids (1-3). Compounds 1 and 2, designated as monanchosterols A and B, respectively, represent the first examples of steroids possessing the bicyclo[4.3.1] A/B ring system from a natural source. Compounds 1-3 were investigated for their anti-inflammatory activity by evaluating their inhibitory effects on the mRNA expression of IL-6, TNF-α, and COX-2 in the LPS-stimulated murine RAW264.7 macrophage cells. Compounds 2 and 3 exhibited significant inhibitory effects on the mRNA expression of IL-6 without notable cytotoxicity to the cells in a dose-dependent manner.

The Halicylindramides, Farnesoid X Receptor Antagonizing Depsipeptides from a Petrosia sp. Marine Sponge Collected in Korea.

Three new structurally related depsipeptides, halicylindramides F-H (1-3), and two known halicylindramides were isolated from a Petrosia sp. marine sponge collected off the shore of Youngdeok-Gun, East Sea, Republic of Korea. Their planar structures were elucidated by extensive spectroscopic data analyses including 1D and 2D NMR data as well as MS data. The absolute configurations of halicylindramides F-H (1-3) were determined by Marfeys method in combination with Edman degradation. The absolute configurations at C-4 of the dioxyindolyl alanine (Dioia) residues of halicylindramides G (2) and H (3) were determined as 4S and 4R, respectively, based on ECD spectroscopy. The C-2 configurations of Dioia in 2 and 3 were speculated to both be 2R based on the shared biogenesis of the halicylindramides. Halicylindramides F (1), A (4), and C (5) showed human farnesoid X receptor (hFXR) antagonistic activities, but did not bind directly to hFXR.

Acredinone C and the Effect of Acredinones on Osteoclastogenic and Osteoblastogenic Activity

A new inhibitor, acredinone C (1), of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation was isolated from the culture broth of the fungus Acremonium sp. (F9A015) along with acredinones A (2) and B (3). The structure of acredinone C (1), which incorporates benzophenone and xanthone moieties, was established by the analyses of combined spectroscopic data including 1D and 2D NMR and MS. All of the acredinones studied efficiently inhibited the RANKL-induced formation of TRAP(+)-MNCs in a dose-dependent manner without any cytotoxicity up to 10 μM. Acredinone A showed dual activity in both osteoclast and osteoblast differentiation in vitro and good efficacy in an animal disease model of bone formation.