Cytotoxic C₂₁ and C₂₂ Terpenoid-Derived Metabolites from the Sponge <i>Ircinia</i> sp.

One novel C21 terpenoidal natural product, ircinolin A (2), two new C22 furanoterpene metabolites, 15-acetylirciformonin B (3) and 10-acetylirciformonin B (4), and two known compounds, irciformonin B (1) and irciformonin F (5), were isolated from the sponge Ircinia sp. The structures of these compounds were elucidated on the basis of their spectroscopic data. Moreover, the absolute configuration of 1 was determined by Mosher’s method. Among these metabolites, 2 is the first C21 terpenoid-derived metabolite to be reported from this genus. Compounds 1 and 3–5 exhibited significant cytotoxic activity against K562, DLD-1, HepG2, and Hep3B cancer cell lines

Oxygenated Cembranoids from a Formosan Soft Coral <i>Sinularia gibberosa</i>

Chemical investigation of a Formosan soft coral, Sinularia gibberosa, has led to the isolation of eight oxygenated cembranoids, 1−8, including seven new compounds, gibberosenes A−G (2−8). None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. Compound 1 significantly inhibited the accumulation of the pro-inflammatory COX-2 protein of the LPS-stimulated RAW264.7 macrophage cells

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>

Simplexins A−I, Eunicellin-Based Diterpenoids from the Soft Coral <i>Klyxum simplex</i>

Nine new eunicellin-based diterpenoids, simplexins A−I (1−9), were isolated from a Dongsha Atoll soft coral, Klyxum simplex. The structures of these compounds were established by detailed spectroscopic analysis (IR, MS, 1D and 2D NMR) and by comparison with the physical and spectral data of related known compounds. The absolute configuration of 1 was determined by a modified Mosher’s method. Compounds 1, 4, and 5 were found to be cytotoxic toward a limited panel of cancer cell lines. Compound 5 was shown to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells

A C-3 Methylated Isocembranoid and 10-Oxocembranoids from a Formosan Soft Coral, <i>Sinularia grandilobata</i>

Five new cembranoids, designated grandilobatins A−E (1−5), were isolated from the soft coral Sinularia grandilobata. Grandilobatin C (3) was found to have a novel skeleton with the C-4 methyl group of the normal cembranoid rearranged to C-3, while the other metabolites were identified as new 10-oxocembranoids. Metabolite 4 has weak cytotoxicity toward MDA-MB-23 human breast tumor cells. Also, 4 significantly inhibited the accumulation of the pro-inflammatory iNOS protein of LPS-stimulated RAW264.7 macrophage cells at 50 µM

Crassocolides A−F, Cembranoids with a <i>trans-</i>Fused Lactone from the Soft Coral <i>Sarcophyton crassocaule</i>

Six new polyoxygenated cembrane-based diterpenoids possessing a trans-fused α-methylene-γ-lactone, crassocolides A−F (1−6), have been isolated along with the known compound 7 from the ethyl acetate extract of a Taiwanese soft coral, Sarcophyton crassocaule. The structures of 1−6 have been established by detailed spectroscopic analysis, including 2D NMR (1H−H COSY, HMQC, HMBC, and NOESY) spectroscopy, while their absolute configurations were determined using a modified Mosher's method for 1. The structure of 5 was further proven by X-ray diffraction analysis. The full assignment of NMR data of 7 is reported herein for the first time. The cytotoxicity of crassocolides 1−4, 6, and 7 against a limited panel of cancer cells was also determined

Crassocolides A−F, Cembranoids with a <i>trans-</i>Fused Lactone from the Soft Coral <i>Sarcophyton crassocaule</i>

Six new polyoxygenated cembrane-based diterpenoids possessing a trans-fused α-methylene-γ-lactone, crassocolides A−F (1−6), have been isolated along with the known compound 7 from the ethyl acetate extract of a Taiwanese soft coral, Sarcophyton crassocaule. The structures of 1−6 have been established by detailed spectroscopic analysis, including 2D NMR (1H−H COSY, HMQC, HMBC, and NOESY) spectroscopy, while their absolute configurations were determined using a modified Mosher's method for 1. The structure of 5 was further proven by X-ray diffraction analysis. The full assignment of NMR data of 7 is reported herein for the first time. The cytotoxicity of crassocolides 1−4, 6, and 7 against a limited panel of cancer cells was also determined

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>

DataSheet_1_Chemometric-Guided Exploration of Marine Anti-Neurofibroma Leads.pdf

In-depth analysis of metabolomics diversity of marine species through advanced mass spectrometric analysis is one of the most promising new tools for the development of marine drugs against mild and life-threatening diseases. Neurofibromas are a common type of tumor in the peripheral nervous system. Currently, there are very limited treatment options for neurofibromas. In our course of exploring potential therapeutic agents for neurofibroma treatment, the multi-informative molecular networking (MIMN) approach was proposed. The MIMNs of the Lendenfeldia sp. sponge extract and sub-fractions were established according to their inhibitory activity against several inflammatory chemokines (CCL3, CCL4, CCL5, CXCL1, CXCL8, and CXCL10) in neurofibroma cell line hTERT-NF1-ipNF95.11b-C (CRL-3390). The visualized MIMN revealed the anti-inflammatory potential of scalarane-enriched fractions, and the follow-up annotation and isolation led to the identification of a scalarane, 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (2). Our results revealed that the most abundant scalarane (2) dominated the anti-chemokine effect of Lendenfeldia sp. extract together with other scalaranes, indicating the potential application of sponge-derived scalaranes to be developed as therapeutic agents for neurofibromas.</p

Nardosinane Sesquiterpenoids from the Formosan Soft Coral <i>Lemnalia flava</i>

Four new nardosinane-type sesquiterpenoids, flavalins A−D (1−4), have been isolated from the Formosan soft coral Lemnalia flava. The structures of the new metabolites were determined by extensive spectroscopic analysis, and the structure of 2 was confirmed by X-ray diffraction analysis. A plausible biosynthetic pathway to 1 and 2 is proposed. Compound 1 was found to display dose-dependent inhibition of iNOS protein expression, and 1 and 2 were shown to possess significant neuroprotective activity