Eunicellin-Based Diterpenoids from the Formosan Soft Coral <i>Klyxum molle</i> with Inhibitory Activity on Superoxide Generation and Elastase Release by Neutrophils

Eleven new eunicellin-based diterpenoids possessing a cladiellane skeleton with a C-2, C-9 ether bridge, klymollins I–S (<b>1</b>–<b>11</b>), have been isolated from the EtOAc extract of the soft coral <i>Klyxum molle</i> from Taiwan waters. The structures of compounds <b>1</b>–<b>11</b> were elucidated by extensive spectroscopic analysis, including 2D NMR spectroscopy (COSY, HSQC, HMBC, and NOESY). Compound <b>5</b> exhibited cytotoxicity toward several cancer cell lines. Compound <b>5</b> is the first eunicellin-based metabolite bearing a phenyl group and displays significant inhibition of both superoxide anion generation and elastase release in <i>N</i>-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils

Structural Elucidation and Structure–Anti-inflammatory Activity Relationships of Cembranoids from Cultured Soft Corals <i>Sinularia sandensis</i> and <i>Sinularia flexibilis</i>

New cembranoids 4-carbomethoxyl-10-epigyrosanoldie E (<b>1</b>), 7-acetylsinumaximol B (<b>2</b>), diepoxycembrene B (<b>6</b>), dihydromanaarenolide I (<b>8</b>), and isosinulaflexiolide K (<b>9</b>), along with 11 known related metabolites, were isolated from cultured soft corals <i>Sinularia sandensis</i> and <i>Sinularia flexibilis</i>. The structures were elucidated by means of infrared, mass spectrometry, and nuclear magnetic resonance techniques, and the absolute configurations of <b>1</b>, <b>4</b>, <b>9</b>, and <b>15</b> were further confirmed by single-crystal X-ray diffraction analysis. The absolute configurations of these coral metabolites and comparison with known analogues showed that one hypothesis (that cembrane diterpenes possessing an absolute configuration of an isopropyl group at C1 obtained from Alcyonacean soft corals belong to the α series, whereas analogues isolated from Gorgonacean corals belong to the β series) is not applicable for a small number of cembranoids. An <i>in vitro</i> anti-inflammatory study using LPS-stimulated macrophage-like cell line RAW 264.7 revealed that compounds <b>9–14</b> significantly suppressed the accumulation of pro-inflammatory proteins, iNOS and COX-2. Structure–activity relationship analysis indicated that cembrane-type compounds with one seven-membered lactone moiety at C-1 are potential anti-inflammatory agents. This is the first culture system in the world that has successfully been used to farm <i>S. sandensis</i>

Halogenated Sesquiterpenoids from the Red Alga <i>Laurencia tristicha</i> Collected in Taiwan

Chemical investigation of the red alga <i>Laurencia tristicha</i> led to the discovery of eight new halogenated chamigrane-type sesquiterpenoids (<b>1</b>–<b>8</b>) and one new bromocuparane-type sesquiterpene (<b>9</b>), along with nine known related metabolites (<b>10</b>–<b>18</b>). Their structures were elucidated on the basis of extensive spectroscopic analyses, and the absolute configurations of <b>1</b>–<b>8</b> were proposed by comparison to the biosynthetically related known compound <b>12</b>. Cytotoxicity, antibacterial, and anti-inflammatory activities of these isolates were also investigated. The results showed that compound <b>11</b> exhibited good antibacterial activity against <i>Serratia marcescens</i> compared to the positive control ampicillin at a dosage of 100 μg/disk. Compound <b>17</b> showed strong inhibition toward elastase release generation at 10 μM

Halogenated Sesquiterpenoids from the Red Alga <i>Laurencia tristicha</i> Collected in Taiwan

Chemical investigation of the red alga <i>Laurencia tristicha</i> led to the discovery of eight new halogenated chamigrane-type sesquiterpenoids (<b>1</b>–<b>8</b>) and one new bromocuparane-type sesquiterpene (<b>9</b>), along with nine known related metabolites (<b>10</b>–<b>18</b>). Their structures were elucidated on the basis of extensive spectroscopic analyses, and the absolute configurations of <b>1</b>–<b>8</b> were proposed by comparison to the biosynthetically related known compound <b>12</b>. Cytotoxicity, antibacterial, and anti-inflammatory activities of these isolates were also investigated. The results showed that compound <b>11</b> exhibited good antibacterial activity against <i>Serratia marcescens</i> compared to the positive control ampicillin at a dosage of 100 μg/disk. Compound <b>17</b> showed strong inhibition toward elastase release generation at 10 μM

New Meroterpenoids from <i>Aspergillus terreus</i> with Inhibition of Cyclooxygenase‑2 Expression

Two novel meroterpenoids, yaminterritrems A (<b>1</b>) and B (<b>2</b>), were isolated from <i>Aspergillus terreus</i> collected from hot spring zones in Yang-Ming Mountain, Taiwan, and cultured at 40 °C. The structures of <b>1</b> and <b>2</b> were elucidated by NMR, MS spectral and X-ray crystallographic analyses. The biosynthetic route for <b>1</b> and <b>2</b> involving the conversion of the sesquiterpene with phenyl-α-pyrone is proposed. Besides, <b>2</b> exhibited a dose-dependent inhibitory effect on COX-2 expression in LPS-stimulated RAW264.7 macrophages

Bioactive Isoprenoid-Derived Natural Products from a Dongsha Atoll Soft Coral Sinularia erecta

Four new isoprenoids, including two norcembranoids sinulerectols A and B (<b>1</b> and <b>2</b>), a cembranoid sinulerectol C (<b>3</b>), and a degraded cembranoid sinulerectadione (<b>4</b>), along with three known isoprenoids, an unnamed norcembrene (<b>5</b>), sinularectin (<b>6</b>), and ineleganolide (<b>7</b>), and a known nitrogen-containing compound (<i>Z</i>)-<i>N</i>-[2-(4-hydroxyphenyl)­ethyl]-3-methyldodec-2-enamide (<b>8</b>), were isolated from an extract of the marine soft coral Sinularia erecta. The structure of sinularectin (<b>6</b>) was revised, too. Compounds <b>3</b>, <b>4</b>, and <b>8</b> exhibited inhibitory activity against the proliferation of a limited panel of cancer cell lines, whereas <b>1</b>, <b>2</b>, and <b>8</b> displayed potent anti-inflammatory activity in fMLP/CB-stimulated human neutrophils

Withanolide-Based Steroids from the Cultured Soft Coral <i>Sinularia brassica</i>

Seven novel withanolides, sinubrasolides A–G (<b>1</b>–<b>7</b>), have been isolated from the cultured soft coral <i>Sinularia brassica</i>. The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of <b>1</b> was established by X-ray crystallographic analysis. The cytotoxicities of compounds <b>1</b>–<b>7</b> against a limited panel of cancer cell lines also were determined

Withanolide-Based Steroids from the Cultured Soft Coral <i>Sinularia brassica</i>

Seven novel withanolides, sinubrasolides A–G (<b>1</b>–<b>7</b>), have been isolated from the cultured soft coral <i>Sinularia brassica</i>. The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of <b>1</b> was established by X-ray crystallographic analysis. The cytotoxicities of compounds <b>1</b>–<b>7</b> against a limited panel of cancer cell lines also were determined

A Soft Coral-Derived Compound, 11-<i>epi</i>-Sinulariolide Acetate Suppresses Inflammatory Response and Bone Destruction in Adjuvant-Induced Arthritis

<div><p>In recent years, a significant number of metabolites with potent anti-inflammatory properties have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we isolated 11-<i>epi</i>-sinulariolide acetate (Ya-s11), a cembrane-type compound with anti-inflammatory effects, from the Formosa soft coral <i>Sinularia querciformis</i>. Preliminary screening revealed that Ya-s11 significantly inhibited the expression of the proinflammatory proteins induced nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated murine macrophages. We also examined the therapeutic effects of Ya-s11 on adjuvant-induced arthritis (AIA) in female Lewis rats, which demonstrate features similar to human rheumatoid arthritis (RA). Animal experiments revealed that Ya-s11 (subcutaneously 9 mg/kg once every 2 days from day 7 to day 28 postimmunization) significantly inhibited AIA characteristics. Moreover, Ya-s11 also attenuated protein expression of cathepsin K, matrix metalloproteinases-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor-α (TNF-α) in ankle tissues of AIA-rats. Based on its attenuation of the expression of proinflammatory proteins and disease progression in AIA rats, the marine-derived compound Ya-s11 may serve as a useful therapeutic agent for the treatment of RA.</p></div