Chiung Yao Huang

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.

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.

Bioactive Cembranoids from the Soft Coral Sinularia crassa

Eight new cembranoids, crassarines A–H (1–8) were isolated from the Formosan soft coral Sinularia crassa. Compounds 1–3 represent the rare cembranoids with a 1,12-oxa-bridged tetrahydrofuran ring, while 4 and 5 are the firstly discovered 1,11-oxa-bridged tetrahydropyranocembranoids. The absolute configuration of 6 was determined using the Mosher’s method. Compounds 6 and 8 were found to significantly inhibit the expression of both pro-inflammatory iNOS and COX-2 proteins at 10 μM, respectively, while compounds 4–8 were found to be non-cytotoxic toward the selected human liver cancer 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.

Steroids from the Soft Coral Sinularia crassa

One new sterol, crassarosterol A (1), and four new steroidal glycosides, crassarosterosides A–D (2–5) were isolated from the Formosan soft coral Sinularia crassa. The absolute configuration of 1 was determined using the Mosher’s method. The absolute configurations for the sugar moieties of 2–5 were determined by HPLC analysis on the o-tolylthiocarbamates derived from the liberated sugar after acid hydrolysis. Compounds 2 and 4 could significantly inhibit the expression of pro-inflammatory iNOS protein at 10 µM. In contrast, 1–3 were found to stimulate the expression of COX-2 protein at this concentration. Steroids 1 and 4 also showed cytotoxicity toward the selected human liver cancer cells.

A soft coral natural product, 11-episinulariolide acetate, inhibits gene expression of cyclooxygenase-2 and interleukin-8 through attenuation of calcium signaling

Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancer cells. EGFR-mediated signaling involves inflammatory gene expression including cyclooxygenase (COX)-2 and interleukin (IL)-8, and is associated with cancer pathogenesis. In a search of phytochemicals with anti-inflammatory activity, the COX-2 and IL-8 inhibitory activities of some marine compounds were examined. After screening these compounds 11-episinulariolide acetate (1) from soft coral exhibited the most potent activity. Reverse-transcription PCR; western blotting; ELISA and luciferase assays were used to test the effect of compound 1 on EGF-stimulated expressions of COX-2 and IL-8 in A431 human epidermoid carcinoma cells. After exposure to 10 μM of compound 1, expression levels of COX-2 and IL-8 were reduced. In addition; intracellular Ca2+ increase and Ca2+-dependent transcription factor activation were blocked by compound 1. Thus, compound 1 can potentially serve as a lead compound for targeting Ca2+ signaling-dependent inflammatory diseases.

Isoprenoids from the Soft Coral Sarcophyton glaucum

Five new isoprenoids, 3,4,8,16-tetra-epi-lobocrasol (1), 1,15β-epoxy-deoxysarcophine (2), 3,4-dihydro-4α,7β,8α-trihydroxy-Δ2-sarcophine (3), ent-sarcophyolide E (4), and 16-deacetyl- halicrasterol B (5) and ten known compounds 6‒15, were characterized from the marine soft coral Sarcophyton glaucum, collected off Taitung coastline. Their structures were defined by analyzing spectra data, especially 2D NMR and electronic circular dichroism (ECD). The structure of the known compound lobocrasol (7) was revised. Cytotoxicity potential of the isolated compounds was reported, too.

Cubitanoids and Cembranoids from the Soft Coral Sinularia nanolobata

Two new cubitanoids, nanoculones A and B (1 and 2), and three new cembranoids, nanolobols A–C (3–5), as well as six known compounds, calyculone I (6), sinulariuol A (7), sinulariols C, D, H, and J (8–11), were isolated from the soft coral Sinularia nanolobata, collected off the coast of the eastern region of Taiwan. Their structures were elucidated on the basis of extensive spectroscopic analysis. Cytotoxicity of compounds 1–11 was evaluated. The nitric oxide (NO) inhibitory activity of selected compounds was further measured by assay of lipopolysaccharide (LPS)-stimulated NO production in activated RAW264.7 cells. The results showed that none of 1–11 exhibited cytotoxicity against the tested cancer cell lines, whereas compound 8 was found to significantly reduce NO production.