Secondary Metabolites of Marine-Derived Fungi : Natural Product Chemistry and Biological Activity

The objective of this thesis was the investigation of the secondary metabolites produced by selected fungal strains isolated from the marine environment, and the assessment of their biological activity. Predominantly the antioxidant potential of the isolated compounds was assessed. In addition the isolation of endophytic fungi from Egyptian marine algae was performed. Extracts of seven fungal strains, including six algal-derived and one sponge-derived fungus, were investigated chemically. This investigation resulted in the isolation and structure elucidation of 34 pure compounds representing different structural sub-classes within the polyketides i.e. hydroquinones, naphthalenones, xanthones, isobenzofuranones, pyrones, furanones and vertinoide/sorbicillinoid derivatives. Sixteen compounds (1-8, 12, 13, 17, and 22-26) proved to be new natural products. The structurally unusual hydroquinone derivative acremonin A (1) and acremonin A glucoside (2) were isolated from Acremonium sp. and proved to be a new structural type of natural products. Compound 1 has significant antioxidant activity. Additionally, two naphthalenone stereoisomers (3 and 4) were obtained from this fungus. Compound 5 was isolated for the first time as a natural product and its structure was proven by x-ray analysis. In addition to these compounds an inseparable mixture of three new isomeric compounds (6-8) was analysed. Two new xanthone derivatives (12 and 13) were isolated from the rare fungal strain Wardomyces anomalus. These compounds showed an interesting new oxygenation pattern. Compound 12 has significant DPPH radical scavenging effects, and is also able to inhibit peroxidation of linolenic acid. Significant TK p56 lck enzyme inhibitor activity is also observed for 12. From Epicoccum sp., a new isobenzofuranone derivative (17) was isolated. Epicoccone (17) has potent antioxidant activity.The sponge-derived fungus Trichoderma viride contained four unprecedented and most structurally unusual sorbicillinoid derivatives (22-25), together with a new pyrone derivative (26). To date reports concerning antioxidant metabolites from marine fungi are very rare. This study demonstrates that marine fungi are an excellent source for the discovery of novel antioxidant derivatives. Besides the prominent biological activity the diversity of structures obtained during this project is a further motivation for the investigation of marine-derived fungi