In order to search for bioactive compounds from the organic extracts of a Formosan soft coral Lemnalia flava fourteen natural compounds, including seven new nardosinane sesquiterpenoids flavalin B-H (1-7), two new nornardosinane sesquiterpenoids flavalins I-J (8-9), along with five known compounds, 2-oxolemnacarnol (10), lemnacarnol (11), armatin F (12), (2R)-2-hydroxylemnal-1(10)-en-12-one (13) and laevinol B (14) were isolated from L. flava. The structures of these compounds were established by the detailed spectral analysis (IR, MS, 1D, 2D NMR) and by comparison of the spectral data with those of the related known compounds. The structure of 1 was unambiguously proven by X-ray diffraction analysis. The absolute configuration of 13 was further determined by a modified Mosher's method. The neuroprotective effect compounds of 1¡V3 against the damage of 6-hydroxydopamine (6-OHDA) toward SH-SY5Y cells was also measured. The cytotoxicity of 6-OHDA on SH-SY5Y cells was significantly reduced by pretreatment of 1 at various concentrations. The cytotoxicity of compounds 1¡V13 against human breast carcinoma (MCF-7), human colon carcinoma (WiDr), human laryngeal carcinoma (HEp 2), human medulloblastoma (Daoy) T-cell acute lymphoblastic leukemia(CCRF-CEM), colon adenocarcinoma (DLD-1), human promyelocytic leukemia (HL-60) and murine leukemia (P388D1) cell lines was studied. The ability of 1¡V13 to inhibit the up-regulation of pro-inflammatory iNOS (inducible nitric oxide synthase) and COX-2(cyclooxygenase-2) proteins in LPS (lipopolysaccharide)-stimulated RAW264.7 macrophage cells was examined, and it was shown that no cytotoxic and anti-inflammatory activity could be found for these compounds.

This dissertation mainly discussed the investigation of three different kinds of Formosan soft corals, Cespitularia hypotentaculata Roxas, C. taeniata May and Junceella juncea, as well as Formosan star-anise, Illicium arborescens Hayata. Their EtOAc extracts were investigated by intensive chromatography. Twenty new natural products were isolated and purified and their biological activities were studied. The chemical investigation of soft coral Cespitularia hypotentaculata and C. taeniata resulted in the isolation of twenty natural products, including ten new natural products, designated as cespihypotins B, W¡VZ (6, 1 ¡V 4), cespihypotone (5), cespitaenins A (10) and F-H (7-9) as well as fourteen know compounds (21-34). Compounds 1-3 were nor-verticillane-type nor-diterpenes. Compounds 4-6 were verticillane-type diterpenes. Cespitaenins A and F (10 & 7) were nor-verticillane-type nor-diterpenes. Cespitaenins G and H (8 & 9) were verticillane-type diterpenes. Three new briarane-type natural products, juncenolides L-N¡]11-13¡^ toghther with and one know compound (35) were isolated from Junceella juncea. The study of Formosan star anise, Illicium arborescens Hayata has afforded seven new compounds (14-20). Two of them were stereoisomer, named 2,3-dide- hydro-5-O-methyl-11-epiillifunone E (14) and 2,3-Didehydro-5-O-methylillifunone E (15). The others were 8,9-secoprezizaane-type sesquiterpenes (16-20). All the structures of above compounds were elucidated by physical and spectroscopic analyses (IR, mass, UV, optical rotation and NMR), and also by comparisions with the published data. Cytotoxicity and in vitro anti-inflammatory activities were measured by Dr. Yao-Haur Kuo of National Research Institute of Chinese Medicine and Dr. Tsong-Long Hwang of Chang Gung University. The biological activities of compounds against MCF-7 (Human breast adenocarcinoma), Doay (Human medulloblastoma), WiDr (Human colon adenocarcinoma), Hela (Human cervical epitheloid carcinoma) cell lines and effects of compounds on superoxide anion generation and elastase release by human neutrophils in response to FMLP/CB. were tested. The effects of compounds 9-12 on superoxide anion generation and elastase release by human neutrophils in response to FMLP/CB were 6.19, 6.72, 7.56 and 6.72 respectively. The IC50 of compounds 14 and 19 against MCF-7, Doay, WiDr and Hela were 9.0, 7.1, 11.2, 10.9 and 5.1, 6.3, 10.9, 6.24 £gg/mL, respectively.

Abstract Investigation on the chemical constituents of EtOH extract of the Formosan soft coral Sinularia grandilobata, collected off the Kenting coast, has led to the isolation of six cembrane-type diterpenoids, grandilobatins A-F (1-6), and four steroids, sinugrandisterols A-D (7-10). All metabolites 1-10 are new natural products. The structures of 1-10 were elucidated by the analysis of spectroscopic data (MS, IR, 1D and 2D NMR) and by comparison of the related spectral data with those of related metabolites in literatures. The cytotoxicity assays of compounds 1-10 against the growth of cell lines, including MDA-MB-231(human breast cancer cell), MCF 7 (human breast cancer cell), Hep G2 (human liver carcinoma), and A-549 (human lung carcinoma), were carried out. The result showed that compound 5 exhibited moderate cytotoxicity against MDA-MB-231 cells. Compounds 7 and 8 showed moderate cytotoxicity against Hep G2 and MDA-MB-231 tumor cells and exhibited weak cytotoxicity against A-549 and MCF 7 tumor cells. Compound 9 showed weak cytotoxicity against A-549 and MCF 7 tumor cells.

No description available.

In order to discover for bioactive compounds, we have studied the chemical constituents from the organic extracts of soft coral Klyxum molle. This study had led to the isolation of 16 eunicellin-type diterpenoids, including ten new compounds, klymollins A¡VJ (1¡V10), along with six know compounds 11¡V16. The structures of compounds 1¡V16 were established by spectroscopic methods and by comparison of the spectral data with those of the related known compounds. It is noteworthy to mention that compounds 1¡V10 represent the first example of eunicellins possessing a C-11/C-17 epoxide. The absolute configuration of 4 was determined using a modified Mosher¡¦s method. The cytotoxicity of compounds 1¡V8 and 11¡V16 against the A549 (human lung epithelial cells), HepG2 (human hepatocellular carcinoma), Hep3B (human hepatocellular carcinoma), MCF-7 (human breast adenocarcinoma)¡BMDA-MB231 (human breast adenocarcinoma) tumor cell lines were determined. Compound 11 showed cytotoxicity toward A549 tumor cells (IC50 value of 3.14 £gg/mL) and compounds 15 and 16 were found to exhibit cytotoxicity toward HepG2 tumor cell (IC50 values of 3.82 and 2.50 £gg/mL). Compounds 6 and 7 were found to show significant activity against the accumulation of the pro-inflammatory iNOS and COX-2 protein at 1 £gM.

Eighteen eunicellin-based diterpenoids were isolated from the organisms of the soft coral Cladiella krempfi. According to the results of 1D and 2D NMR spectroscopic experiments, the structures of these marine natural products were established. Among them, krempfielins A¡VJ (1¡V10) are new compounds, and sclerophytin B (11), sclerophytin F (12), litophynols A (13), (1R*, 2R*, 3R*, 6S*, 7S*, 9R*, 10R*, 14R*)-3-butanoyloxycladiell-11(17)-en-6,7-diol (14), litophynin I monoacetate (15), (1R*, 2R*, 3R*, 6S*, 9R*, 10R*, 14R*)-3- acetoxycladiell-7(16)-11(17)-dien-6-ol (16), 6-acetoxy litophynin E (17) and litophynin F (18) are the previously isolated compounds. The anti-inflammation activity of these compounds at 10 £gM was studied. The results showed that 9, 14 and 17 effectively inhibited more than 80% expression of iNOS protein in LPS stimulated RAW 264.7 macrophage cells, and 5, 6, 10, 13 and 18 inhibited more than 60% expression of iNOS protein. Also, 9, 12, 16 and 18 were found to inhibit the expression of COX-2 protein in LPS stimulated RAW 264.7 macrophage cells to 52.5, 79.2, 82.2 and 48.2%. Cytotoxicity of these compounds were tested by the MTT assay using five human cancer cell lines (A549, BT483, H1299, Hep3B and SAS) and one normal cell line, BEAS2B. Compounds 9, 10, 11, 14, 17 and 18 were shown to exhibit cytotoxic activity.

In order to discover bioactive secondary metabolites, we have studied the chemical constituents from the organic extracts of soft coral Sinularia flexibilis. This study had led to the isolation of eighteen natural compounds 1¡V18, including seven new cembrane-type diterpenoids, flexibilisolides C¡VG (1, 2, 3, 6, 7), flexiblilisin C (5), 11,12-secoflexibillin (4) along with eleven know compounds. The structure of compounds 1¡V18 were established by detailed spectral data analysis (IR, MS, 1D, 2D NMR) and by comparison of the spectral data with those of the related known compounds. The cytotoxicity of compounds 1¡V6, 8¡V14, 16¡V18 against the Hela (human cervical epitheloid carcinoma), SK-Hep1 (human liver carcinoma), and B16 (human melanin carcinoma) tumor cell lines were screened. Compounds 1, 9, 12, and 13 showed moderate activity toward the Hela and SK-Hep1 tumor cells. Compound 12 also showed moderate activity toward the B16 cells, and compound 14 showed activity toward the Hela cells. On the other hand, compounds 1, 9, 13, and 17 were found to show significant activity against the accumulation of the pro-inflammatory iNOS and COX-2 protein at 10 £gM. Compounds 2¡V4, 7, 8, 10, 14, 16 were found to show activity against the accumulation of the pro-inflammatory iNOS protein at 10 £gM.

In order to search for bioactive compounds, we have studied the chemical constituents from the organic extracts of soft coral Klyxum molle. In this study, fifteen eunicellin-type diterpenoids, including eleven new compounds, klymollins K¡VU (1¡V11), along with four known compounds 12¡V15 were isolated. Compounds 16 and 17 were prepared by chemical synthesis. The structures of all compounds were established by spectroscopic methods and comparing the spectral data with known compounds. Compound 5 represents the first eunicellin-type compound with phenylacetyl group. The cytotoxicity of compounds 1¡V17 against K562 (human erythro myeloblastoid leukemia), Molt-4 (human acute lymphoblastic leukemia), and T47D (human breast earcinoma) were determined. Compounds 1, 2, and 3 exhibited weak cytotoxicity against Molt-4 (with ED50 11.52 ¡Ó 2.75, 20.41 ¡Ó 2.92, and 13.11 ¡Ó 3.87 £gg/mL). Compound 5 was found to exhibt significant cytotoxicity toward K562, Molt-4, and T47D (with ED50 4.32 ¡Ó 1.38, 2.36 ¡Ó 0.34, and 4.65 ¡Ó 0.93 £gg/mL). Compound 5 also displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils at 10 £gg/mL (with Inh % 81.56 ¡Ó 3.23, and 89.16 ¡Ó 5.77).

Chromotographic separations of Formosan soft coral Sarcophyton crassocaule (GN-55) led to the isolations of four diterpenes, sarcophine (1), sarcophytoxide (2), (7R*, 8S*)-dihydroxysarcophytonin A (3), sarcophtonin A (4), one steroid, 17

The methylene chloride and acetone extracts of Formosan soft coral Clavularia violacea (Collected at Green Island) were found to exhibit significant cytotoxicity against P-388, A-549 and HT-29 cancer cell lines. Chromatographic separation let to the isolation of one prostanoid, 1, two cembranoid deterpenes, 2 and 3, one aromadedrane-type sesquiterpene, 4, one neodollabellane diterpene, 5, (+)-curcuphenol, 6 and two sesquiterpene lactones, 7 and 8. Compounds 1, 2, 4, and were new compounds. Compounds 1-5 exhibited significant cytotoxicity against P-388, HT-29 and A-549 cancer cell.