Thesis (M.Sc.)--Chulalongkorn University, 2008

The objective of this research is to investigate production of anticancer metabolites from the endophtytic Xylaria sp. PB-30 isolated from the healthy and mature leaves of Sandoricum koetjape. After culture grown on five basal media including Malt Extract Broth (MEB), Malt Czapek Broth (MCzB), Corn Meal Broth (CMB), Yeast Extract Sucrose Broth (YEB) and Sabouraud’s Dextrose Broth (SDB). It was found that anticancer metabolites of culture on MEB were produced more than on MCzB, SDB, YEB, CMB and most of them contained in EtOAc extract of broth and mycelia. From 1H-NMR analysis hexane extract of mycelia and broth cultured on mainly contained triglycerides while methanol extracts mainly contained glucose. Metabolites of this fungus exhibiting anticancer activity were produced during stationary phase of growth which was within 35 days of cultivation. Thus EtOAc extract of broth from culture on SDB 27 day, MCzB 35 day, MEB 35 day and EtOAc extracts of mycelia on MEB 35 day were tested for in vitro cytotoxicity activity against cancer cell lines. The EtOAc extracts of broth from culture on MEB showed the highest cytotoxicity activity against all cancer cell lines. The metabolites produced by the endophytic fungus xylaria sp. PB-30 was isolated to afford 5 compounds including (4S,5S,6S)- 5,6-epoxy-4-hydroxy-3-methoxy-5-methyl-cyclohex-2-en-1-one 1, compound 2, cytochalasin D 3, 4-hydroxymellein 4 and 2-hydroxy-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione 5. Cytotoxic activities of compound 1-5 were examined against 5 cell lines including BT474 (breast), CHAGO (lung), HEP-G2 (hepatoma), KATO-3 (gastric), SW620 (colon). Compound 4 was inactive against all cancer cell lines. Compound 1 exhibited cytotoxic activity against all cancer cell lines and was selective against HEP-G2, KATO-III and SW620 with the IC50 values 6.25, 5.61 and 5.31µg/ml, respectively. Compound 2 exhibited cytotoxicity activity against all cancer cell lines and was selective against CHAGO, HEP-G2, KATO-III and SW620 with the IC50 values 6.09, 5.79, 5.41 and 5.49 µg/ml, respectively. Compound 3 exhibited cytotoxicity activity against HEP-G2 and SW 620 with the IC50 values of 6.29 and 6.81µg/ml respectively, and inactive against other cell lines. Compound 5 exhibited only cytotoxicity activity against HEP-G2 with the IC50 value of 3.39 µg/ml