ABSTRACT Marine sponges have proved to be a rich source of new bioactive products. In our screening of several species of Taiwanese marine sponges from southern coast of Taiwan, we have isolated nine new compounds in which one has a new carbon skeleton. Investigation of the marine sponge Parahigginsia sp. has resulted in the isolation of six new sesquiterpenes, parahigginols A-D (59-62), parahigginine (63) and para- higginic acid (65). Two new sesquiterpenes hydroquinones, hippochro- mins A and B (71, 72) were isolated from the marine sponge Hippo- spongia metachromia. In addition, an unstable, novel meroditerpenoid, strongdurin (76), which might be a precursor of strongylophorins, was isolated from the sponge Strongylophora durissima. Moreover study of the secondary metabolites of sponge Theonella cf. swinhoei, four trideca- peptide lactones theonellapeptolides Ia-Id (44-47) and one dimeric ma- crolide swinholide A (49), were also isolated and their structures were determined. The structures of these compounds and their derivatives were established primarily on the basis of their spectral analysis and chemical derivatization. The application of NMR techniques included 1H, 13C NMR, DEPT, COSY, HMQC, HMBC, NOESY and so on. Biological studies revealed that parahigginols A-D (59-62), parahig- ginine (63), parahigginone (64) and parahigginic acid (65), exhibited in vitro cytotoxicity against mouse leukemia cells (P-388) and human mouth epidermoid carcinoma (KB16), lung carcinoma (A549) and colon carci- noma (HT-29) cancer cells. Compounds 60-65 exhibited moderate activity with IC50 value greater than 1 £gg/mL, while parahigginol A (59) was inactive. In our measurement, strongdurin monomethylate (77), which isolated from the marine sponge Strongylophora durissima, was mild cytotoxicity against human mouth epidermoid carcinoma (KB16) and hepatoma carcinoma (Hepa) cell lines with IC50 values of 6.7 and 8.7 £gg/mL. Compounds 13, 14, 68 and 69, which isolated from the marine sponge Hippospongia metachromia, exhibited potent cytotoxicity against human colon (COLO-250) tumor cells at concentrations of 0.10, 0.26, 0.53 and 0.22 £gg/mL, respectively. Theonellapeptolides Ia-Ib (44-45) and swinholide A (49), which isolated from the marine sponge Theonella cf. swinhoei, showed significant cytotoxicity against above NUGC and HONE-1 cell lines at concentrations of 50 £gg/mL, but were inactive at 10 £gg/mL.

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Six new compounds, irciformonins E~J (1~6), were isolated from CH2Cl2/MeOH extract of the sponge Ircinia formosana collected in Taiwan, toghther with two known compounds, irciformonins A and B. These compounds possess a linear C-22-sesterterpenoids type skeleton. The structures of all compounds were elucidated by spectroscopic analysis including 1D and 2D-NMR, optical rotation, IR, UV and high resolution mass spectra, as well as comparison with those in references. The stereochemistry of these compounds were determined by NOESY experiments, MM2 minimized energy, as well as comparison with those in references. The structures of all compounds possess a furan ring, a five membered lactone ring , and three methyl groups. Compounds 1 and 2 are geometric isomers. The differences between them are the substituents of the methoxyl group and the double bond. Compounds 1 and 2 possess substituents of the methoxyl group at C-10 and C-12 and have the double bond at C-11/C-12 and C-10/C-11. The differences between compounds 3 and 6 are the functional groups of the acetyl moeity and the double bond. Compound 3 has an acetyl group at C-12. Compounds 3 and 6 contain two double bonds at C-10/C-11 and C-11/C-12. Compound 4 has a cyclopentane between C-12~C-15 and a ketone group at C-10 while compound 5 possesses two acetyl groups at C-10 and C-15 positions.

The sponge Halichondria okadai is one of the most common sponges in the intertidal zone in Peng-Hu, Taiwan. And their juveniles are found on the back side of rocks in the period of July to October. In the present study, changes of juvenile morphology with their growth and the contents of photoprotective materials were examined. In adults, the thickness of the black surface layer did not correlate with their surface area. In juveniles, changes of their color were not correlated with their surface area neither. In juveniles, the structure of the tissues in the mesoyl layer were looser than the surface layer and there were more black chromatocytes in the surface layer than the mesohyl layer. The compositions of spicules were different in various stages of the sponge. There were no spicules in embryos and larvae. In juveniles, microscleres were the main components. However, megascleres of oxea and strongyle were the major types in adult. When the juveniles exposed to different light treatments, their color changed gradually from white to black. In adults, the total contents of melanin were more in the surface layer than the mesoyl layer. And comparison, the contents of melanin were more in adults (0.074-0.115 mg/protein) than in juveniles (0.028-0.036 mg/protein).

This study documents the marine sponge fauna (Phylum Porifera) in the Northwest Atlantic, through the used of fishermen’s local ecological knowledge, fisheries observer data, trawl survey data and in situ exploration. A review of the role of structural benthic species, including ascidians, bryozoans, corals, hydroids and sponges as ecosystem engineers provides the context within which to discuss the contribution of sponges to seafloor habitat heterogeneity. Fishermen’s knowledge is useful in identifying areas of high concentration of benthic structural species, but is not particularly useful in determining the distribution of specific sponge species, with the exception of glass sponges, with the common name “Russian Hat”. Fisheries observer data from the Scotia Fundy Region and trawl survey data from the Newfoundland Region were obtained from the years 1977-2001 and 1973-2007 respectively. Despite the lack of systematic collection of information on sponge catches, prior to 2002, the information recorded show broad scale patterns of sponge distribution from the Scotian Shelf to the Eastern Arctic, and this thesis brings this information together for the first time. The move to deeper and more northern waters following the groundfish collapse in 1992 resulted in large catches of sponges, up to 5000kg per set, on the Labrador Shelf and Eastern Arctic. The combination of fishermen’s information, observer data and in situ research on the Scotian Shelf resulted in the identification of a previously undescribed and globally unique population of Vazella pourtalesi, a Hexactinellid sponge, in the Family Rossellidae. The impacts of fishing on the sponge community of the Gulf of Maine were examined by quantifying the sponge community inside and outside of the Western Gulf of Maine Closed Area. After two years, the sponge community within the closed area was dominated by the demosponge, Iophon sp. while the area that remained open to fishing had a higher diversity of sponges. The information presented in this thesis can inform marine ecosystem management, particularly in light of international obligations to protect vulnerable marine ecosystems.

Bioassay guided fractionation of a crude extract of the marine sponge Neopetrosia exigua resulted in the first reported isolation of exiguamines A and B. These pyrroloquinone alkaloids have an unprecedented hexacyclic skeleton that has not been previously encountered in natural products. Biological studies have identified exiguamine A as a potent in vitro inhibitor of the enzyme indoleamine-2,3-dioxygenase (IDO). IDO is an enzyme expressed by tumor cells to evade the immune system. Inhibitors against this enzyme may allow the immune system to attack cancer cells, making this enzyme a potential drug target for anti-cancer agents. Investigation of the crude extract of a Bacillus sp. collected in Dominica led to the isolation of the known diketopiperazine cyclo(S-Val-S-Phe) (3.9). In vitro biological studies revealed that cyclo(S-Val-S-Phe) is able to promote neurite outgrowth, even in the presence of physiological inhibitors. In vivo studies have shown that cyclo(S-VaI-S-Phe) is able promote sprouting in serotonergic and adrenergic axons. Synthesis of the other three diastereomers led to the discovery that cyclo(R-Val-R-Phe) is also an in vitro activator of axonal outgrowth. Inhibitors of the G2 checkpoint are able to increase the cytotoxicity of DNA damaging chemotherapeutics. Bioassay guided fractionation of an extract of the South American plant Duguetia odorata led to the isolation of the G2 checkpoint abrogator, oliveroline. This investigation also led to the isolation of the previously unreported alkaloid N-methylguatterine, and the known alkaloids dehydrodiscretine and pseudopalmatine. Chemical investigation of the marine sponge Myrmekioderma granulatum led to the isolation of the new compounds abolenone and myrmekioside C, as well as the known compounds curcudiol, curcuphenol, abolene and sesquiterpenoid. Biological studies of these compounds revealed that curcudiol is a ligand of the sex hormone-binding globulin. This protein is involved in transporting and regulating the concentration of steroids such as testosterone and estradiol. Many pathological conditions have a lower plasma concentration of these steroids. Ligands to SHBG can release steroids into the blood, so this protein is a potential drug target to treat conditions where a hormone insufficiency is present.

ABSTRACT The marine sponge Xestospongia sp. was collected along seashore area of Lan Yu in Taiwan. Fractionation of the MeOH/CHCl3 extract by using silica gel colum chromatography yielded eight polycycle quinones and hydroquinones ,namely halenaquinone (1)¡B halenaquinol(2)¡B14-methoxyxestoquinone (3)¡B15-methoxyxeatoquinone (4)¡B xestoquinone (5)¡B15-chloro-hydroxestoquinone (6) ¡Badociaquinone A (7)¡B adociaqunone B (8) . The structures of these compounds were idenified by UV¡BIR¡BMS¡B 1D and 2D NMR . Biological screening revealed that compounds 7 and 8 possessed in vitro cytotoxicities against two tumor cell lines (KB 16, HEPA-3B). The ED50 value of compound 7 showed cytotoxicities against KB 16 and HEPA-3B tumor cell lines were 0.26 £gg/mL and < 0.1 £gg/mL, respectively. The ED50 value of compound 8 were < 0.1 £gg/mL and 1.8 £gg/mL .

Bioassay guided fractionation of a crude extract of the marine sponge Neopetrosia exigua resulted in the first reported isolation of exiguamines A and B. These pyrroloquinone alkaloids have an unprecedented hexacyclic skeleton that has not been previously encountered in natural products. Biological studies have identified exiguamine A as a potent in vitro inhibitor of the enzyme indoleamine-2,3-dioxygenase (IDO). IDO is an enzyme expressed by tumor cells to evade the immune system. Inhibitors against this enzyme may allow the immune system to attack cancer cells, making this enzyme a potential drug target for anti-cancer agents. Investigation of the crude extract of a Bacillus sp. collected in Dominica led to the isolation of the known diketopiperazine cyclo(S-Val-S-Phe) (3.9). In vitro biological studies revealed that cyclo(S-Val-S-Phe) is able to promote neurite outgrowth, even in the presence of physiological inhibitors. In vivo studies have shown that cyclo(S-VaI-S-Phe) is able promote sprouting in serotonergic and adrenergic axons. Synthesis of the other three diastereomers led to the discovery that cyclo(R-Val-R-Phe) is also an in vitro activator of axonal outgrowth. Inhibitors of the G2 checkpoint are able to increase the cytotoxicity of DNA damaging chemotherapeutics. Bioassay guided fractionation of an extract of the South American plant Duguetia odorata led to the isolation of the G2 checkpoint abrogator, oliveroline. This investigation also led to the isolation of the previously unreported alkaloid N-methylguatterine, and the known alkaloids dehydrodiscretine and pseudopalmatine. Chemical investigation of the marine sponge Myrmekioderma granulatum led to the isolation of the new compounds abolenone and myrmekioside C, as well as the known compounds curcudiol, curcuphenol, abolene and sesquiterpenoid. Biological studies of these compounds revealed that curcudiol is a ligand of the sex hormone-binding globulin. This protein is involved in transporting and regulating the concentration of steroids such as testosterone and estradiol. Many pathological conditions have a lower plasma concentration of these steroids. Ligands to SHBG can release steroids into the blood, so this protein is a potential drug target to treat conditions where a hormone insufficiency is present.

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