Flexibilins A–C, New Cembrane-Type Diterpenoids from the Formosan Soft Coral, Sinularia flexibilis

Hu, Li-Chung; Su, Jui‐Hsin; Chiang, Michael Y.; Lu, Mei‐Chin; Hwang, Tsong‐Long; Chen, Yung-Husan; Hu, Wan‐Ping; Lin, Nai-Cheng; Wang, Wei‐Hsien; Fang, Lee‐Shing; Kuo, Yueh‐Hsiung; Sung, Ping‐Jyun

doi:10.3390/md11061999

Cited by 16 publications

(7 citation statements)

References 42 publications

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“…The structure and absolute stereochemistry of 9 were also confirmed by single-crystal X-ray diffraction ( Figure 2) with Cu Kα irradiation [Flack parameter of 0.09 (3)] (CCDC 1044093). On the basis of the results presented above, compound 9 was established as (1R,4R,5R,13S,8E,11Z)-5-acetoxy-13-hydroxy-cembr-8(9),11 (12),15(17)-trien-16,4-olide In addition, the 11 known compounds obtained were identified as sinumaximol B (3), 17 pukalide (4), 21 10-epigyrosanoldie E (5), 14,15 diepoxycembrene A (7), 17 sinulaflexiolide K (10), 22 (−)-sandensolide (11), 23 11-dehydrosinulariolide (12), 24 sinulariolide (13), 25 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide (14), 26 dendronpholide F (15), 27 and dendronpholide G (16) 24 by comparison of spectroscopic data with published values. The absolute configurations of 4 and 15 were confirmed by single-crystal X-ray diffraction analysis with Cu Kα radiation [Flack parameters of 0.12(5) and 0.14(8), respectively] for the first time ( Figure 2).…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

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

Tsai

Chen

Sheu

et al. 2015

J. Agric. Food Chem.

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New cembranoids 4-carbomethoxyl-10-epigyrosanoldie E (1), 7-acetylsinumaximol B (2), diepoxycembrene B (6), dihydromanaarenolide I (8), and isosinulaflexiolide K (9), along with 11 known related metabolites, were isolated from cultured soft corals Sinularia sandensis and Sinularia flexibilis. The structures were elucidated by means of infrared, mass spectrometry, and nuclear magnetic resonance techniques, and the absolute configurations of 1, 4, 9, and 15 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 in vitro anti-inflammatory study using LPS-stimulated macrophage-like cell line RAW 264.7 revealed that compounds 9-14 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 S. sandensis.

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Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

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

Tsai

Chen

Sheu

et al. 2015

J. Agric. Food Chem.

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“…Among several marine resources, we were interested in the soft corals of the genus Sinularia (Family: Alcyoniidae) because they were abundant resources of diterpenoidal metabolites with diverse bioactive functions . Several bioactive compounds and anticancer effects for Sinularia‐derived agents had been accumulated.…”

Section: Introductionmentioning

confidence: 99%

Sinularin induces oxidative stress‐mediated G2/M arrest and apoptosis in oral cancer cells

Tang

Huang

et al. 2017

Environmental Toxicology

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Soft corals-derived natural product, sinularin, was antiproliferative against some cancers but its effect and detailed mechanism on oral cancer cells remain unclear. The subject of this study is to examine the antioral cancer effects and underlying detailed mechanisms in terms of cell viability, oxidative stress, cell cycle analysis, and apoptosis analyses. In MTS assay, sinularin dose-responsively decreased cell viability of three oral cancer cells (Ca9-22, HSC-3, and CAL 27) but only little damage to oral normal cells (HGF-1). This cell killing effect was rescued by the antioxidant N-acetylcysteine (NAC) pretreatment. Abnormal cell morphology and induction of reactive oxygen species (ROS) were found in sinularin-treated oral cancer Ca9-22 cells, however, NAC pretreatment also recovered these changes. Sinularin arrested the Ca9-22 cells at G2/M phase and dysregulated the G2/M regulatory proteins such as cdc2 and cyclin B1. Sinularin dose-responsively induced apoptosis on Ca9-22 cells in terms of flow cytometry (annexin V and pancaspase analyses) and western blotting (caspases 3, 8, 9) and poly (ADP-ribose) polymerase (PARP). These apoptotic changes of sinularin-treated Ca9-22 cells were rescued by NAC pretreatment. Taken together, sinularin induces oxidative stress-mediated antiproliferation, G2/M arrest, and apoptosis against oral cancer cells and may be a potential marine drug for antioral cancer therapy.

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“…Marine organisms are the cradle for many excellent pharmaceutical products, particularly soft corals [ 25 , 26 , 27 ]. Several types of cembranoid compounds with prominent biological activities have been isolated from Sinularia flexibilis [ 28 , 29 , 30 , 31 , 32 ]. Numerous marine metabolites in Taiwanese soft corals have also been found from Sinularia flexibilis , with anti-inflammatory activity [ 31 , 33 ], neuroprotective effect [ 34 ] and cytotoxic activity against various cancer cells lines [ 35 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Sandensolide Induces Oxidative Stress-Mediated Apoptosis in Oral Cancer Cells and in Zebrafish Xenograft Model

Chen

Liu

et al. 2018

Marine Drugs

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Presently, natural sources and herbs are being sought for the treatment of human oral squamous cell carcinoma (OSCC) in order to alleviate the side effects of chemotherapy. This study investigates the effect of sandensolide, a cembrane isolated from Sinularia flexibilis, to inhibit human OSCC cell growth with the aim of developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (Ca9.22, SCC9 and HSC-3 cell lines) and oral normal cells (HGF-1), as well as a zebrafish xenograft model, were used to test the cytotoxicity of sandensolide (MTT assay), as well as to perform cell cycle analysis and Western blotting. Both the in vitro bioassay and the zebrafish xenograft model demonstrated the anti-oral cancer effect of sandensolide. Moreover, sandensolide was able to significantly suppress colony formation and induce apoptosis, as well as cell cycle arrest, in OSCC by regulating multiple key proteins. Induction of reactive oxygen species (ROS) was observed in sandensolide-treated oral cancer cells. However, these apoptotic changes were rescued by NAC pretreatment. These findings contribute to the knowledge of the model of action of sandensolide, which may induce oxidative stress-mediated cell death pathways as a potential agent in oral cancer therapeutics.

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Flexibilins A–C, New Cembrane-Type Diterpenoids from the Formosan Soft Coral, Sinularia flexibilis

Cited by 16 publications

References 42 publications

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

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

Sinularin induces oxidative stress‐mediated G2/M arrest and apoptosis in oral cancer cells

Sandensolide Induces Oxidative Stress-Mediated Apoptosis in Oral Cancer Cells and in Zebrafish Xenograft Model

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