Study On The Secondary Metabolites From Eight Marine-Derived Microbes

This thesis reports the secondary metabolites isolated from eight marine-derived microbes including four actinomycetes isolated from Jiaozhou Bay and four fungi isolated from Porphyra yezoensis. Seventy-eight pure compounds among which ten are novel ones, have been obtained. Some of the pure compounds have been tested of their biological activities. And, some strains have been identified through morphological observation and phylogenetic analysis.Fourty compounds including six novel secondary metabolites have been separated from actinomycetes M491, M097, M361 and M353. Fourteen compounds including two novel sesquiterpenes 15-hydroxy-T-muurolol (1a) and 11,15-dihydroxy-T-muurolol (1b), two novel microbial metabolites T-muurolol (2b) and 3α-hydroxy-T-muurolol (2c), and two novel macrolides chalcomycin C (7) and chalcomycin D (8) have been obtained from M491. 3-Oxo-T-muurolol (2a) was re-isolated and crystalized. The absolute configuration was solved by X-ray spectroscopy and the previously reported structures were corrected. Two novel sesquiterpenes 5-hydroxy-epi-isozizaene (28) and 5,14-dihydroxy-isozizaene (30) and another eight known compounds have been separated from M353. Twelve and three known compounds have been isolated from M097 and M361, respectively.Twelve fungal isolates have been isolated from the Concocelis of Porphyra yezoensis. The dorminant strain N5 produced fifteen compounds including wide-spectrum antibiotics and plant growth-regulators phenylacetic acid (42), p-hydroxyphenylethyl alcohol (43), L-β-phenyllactic acid (49).Fungal strains N27, EF8 and GA4 have been isolated from Porphyra yezoensis with white-spot syndrome. Sixteen compounds including one new urea-derivative hualyzin (62) and three new phenalenones 7-methyl isonorherqueinone (69), 7,8-dimethyl atrovenetin (71) and 8-methyl-deoxyherqueinone (73) have been purified from GA4. Twelve and two known compounds have been separated from N27 and EF8, respectively.Some of the compounds have been tested of their cytotoxicity against thirty-seven human cell tumor lines using MTT method. Chalcomycin C (7) and chalcomycin D (8) exhibited high cytoxicity with the average IC50 of 0.027μg/ml and 0.007μg/mL, respectively. 7,8-Dimethyl atrovenetin (71) and 8-methyl deoxyherqueinone (73) showed moderate cytotoxicity with the IC50 of 5.1μg/mL and 0.7μg/mL, respectively.Besides, some known compounds have been firstly reported for their cytotoxicity: chalcomycin (0.015μg/mL), kalamycin (0.06μg/mL), (+)-homononactic acid (1.9μg/mL), (+)-nonactic acid (2.3μg/mL), griseoviridin (3.9μg/mL), cyclo (L-Trp-L-Phe) (3.3μg/mL), WIN 64821 (5.8μg/mL) and 3,5-dihydroxy-2-methyl-4-pyrone (3.3μg/mL).M353 was identified as Streptomyces sp. N5 belongs to Cladosporium. EF8 belongs to Aspergillus. GA4 and N27 belong to Penicillium.