Jui Hsin Su

Survey of briarane-type diterpenoids - Part IV

The structures, names, biological activities, and references of 137 briarane-type diterpenoids are summarized. All briaranes mentioned in this review article were obtained from various octocorals including the specimens belonging to the genus Briareum, Ellisella, Gorgonella, Junceella, Subergorgia, Renilla, and Pachyclavularia.

Hirsutalins A−H, Eunicellin-Based Diterpenoids from the Soft Coral Cladiella hirsuta

Eight new eunicellin-base diterpenoids, hirsutalins A-H (1-8), were isolated from the soft coral Cladiella hirsuta. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute configuration of 1 was determined by Moshers method. Compounds 1, 5, and 6 have been shown to exhibit cytotoxicity toward several cancer cell lines. Compounds 2-4 and 8 were found to display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein, with compound 2 also effectively reducing the level of COX-2 protein.

A C-3 methylated isocembranoid and 10-oxocembranoids from a formosan soft coral, Sinularia grandilobata.

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 microM.

Klysimplexins I–T, eunicellin-based diterpenoids from the cultured soft coral Klyxum simplex

New eunicellin-base diterpenoids, klysimplexins I-T (1-12), were isolated from a cultured soft coral Klyxum simplex. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute stereochemistry of 4 was determined by Moshers method. Compounds 9 and 12 have been shown to exhibit cytotoxicity toward a limited panel of cancer cell lines. Compounds 2-6, 10 and 11 were found to display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Compounds 10 and 11 also could effectively reduce the level of COX-2 protein.

Oxygenated cembranoids from a Formosan soft coral Sinularia gibberosa.

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.

Hirsutosterols A–G, polyoxygenated steroids from a Formosan soft coral Cladiella hirsuta

Seven new polyoxygenated steroids, hirsutosterols A-G (1-7), were isolated from the Formosan soft coral Cladiella hirsuta. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute configurations of 1 and 5 were determined by Moshers method. Sterols 4-6 possess hydroxy groups at C-9 and C-11 and might be oxidatively cleaved to the corresponding 9,11-secosterols. Hirsutosterol A (1) was found to exhibit a stronger cytotoxicity against a limited panel of cancer cell lines.

Klymollins A-H, bioactive eunicellin-based diterpenoids from the formosan soft coral Klyxum molle.

Eight new eunicellin-based diterpenoids, klymollins A-H (1-8), were isolated during the chemical investigation of the soft coral Klyxum molle from Taiwan waters. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 4 was determined by Moshers method. Bioassays of the new metabolites showed that compounds 3-8 displayed significant in vitro anti-inflammatory activity by inhibiting the expression of the iNOS protein, and compounds 3, 4, and 6-8 also could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.

Briarane Diterpenoids Isolated from Gorgonian Corals between 2011 and 2013

The structures, names, bioactivities and references of 138 briarane-type diterpenoids, including 87 new compounds, are summarized in this review. All the briarane-type compounds mentioned in this review article were obtained from gorgonian corals including the genus Briareum, Dichotella, Junceella and Verrucella. Some of these compounds showed potential bioactivities.

Discovery of New Eunicellins from an Indonesian Octocoral Cladiella sp.

Two new 11-hydroxyeunicellin diterpenoids, cladieunicellin F (1) and (–)-solenopodin C (2), were isolated from an Indonesian octocoral Cladiella sp. The structures of eunicellins 1 and 2 were established by spectroscopic methods, and eunicellin 2 was found to be an enantiomer of the known eunicellin solenopodin C (3). Eunicellin 2 displayed inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils. The previously reported structures of two eunicellin-based compounds, cladielloides A and B, are corrected in this study.

Cracking the Cytotoxicity Code: Apoptotic Induction of 10-Acetylirciformonin B is Mediated through ROS Generation and Mitochondrial Dysfunction

A marine furanoterpenoid derivative, 10-acetylirciformonin B (10AB), was found to inhibit the proliferation of leukemia, hepatoma, and colon cancer cell lines, with selective and significant potency against leukemia cells. It induced DNA damage and apoptosis in leukemia HL 60 cells. To fully understand the mechanism behind the 10AB apoptotic induction against HL 60 cells, we extended our previous findings and further explored the precise molecular targets of 10AB. We found that the use of 10AB increased apoptosis by 8.9%–87.6% and caused disruption of mitochondrial membrane potential (MMP) by 15.2%–95.2% in a dose-dependent manner, as demonstrated by annexin-V/PI and JC-1 staining assays, respectively. Moreover, our findings indicated that the pretreatment of HL 60 cells with N-acetyl-l-cysteine (NAC), a reactive oxygen species (ROS) scavenger, diminished MMP disruption and apoptosis induced by 10AB, suggesting that ROS overproduction plays a crucial rule in the cytotoxic activity of 10AB. The results of a cell-free system assay indicated that 10AB could act as a topoisomerase catalytic inhibitor through the inhibition of topoisomerase IIα. On the protein level, the expression of the anti-apoptotic proteins Bcl-xL and Bcl-2, caspase inhibitors XIAP and survivin, as well as hexokinase II were inhibited by the use of 10AB. On the other hand, the expression of the pro-apoptotic protein Bax was increased after 10AB treatment. Taken together, our results suggest that 10AB-induced apoptosis is mediated through the overproduction of ROS and the disruption of mitochondrial metabolism.