Isolation, Structure Determination and Biological Activity Assessment of Secondary Metabolites from Marine-derived Fungi

The current study focuses on endophytic fungi to be found in marine macroalgae, the secondary metabolites they produce and the biological activities of these metabolites. From 56 algae, 6 marine plants or plants from the intertidal zone, a sponge and a jellyfish a total of 428 fungal strains was isolated representing 45 genera. After large-scale cultivation and extraction of selected fungi, crude extracts were separated using different chromatographic procedures, primarily normal (Si-60) and reversed (RP-18) phase HPLC. All structures were elucidated using spectroscopic methods, mainly 1D and 2D NMR and MS. This investigation resulted in 24 metabolites including 15 novel structures: the unprecedented and structurally unusual compound ascosalipyrrolone A which contains tetramic acid has antiplasmodial activity towards Plasmodium falciparum strains K1 and NF 54. It is also antimicrobially active and inhibits tyrosine kinase p56lck. Additionally, ascosalipyrone was isolated from the obligate marine fungus Ascochyta salicorniae; the sesquiterpenoid compounds drechslerines A-D, 9-hydroxyhelminthosporol, drechslerones A and B, drechslepoxides A and B and drechsleral from the algicolous fungus Drechslera dematioidea. Drechslerine C and Drechsleral have pronounced antiplasmodial activity towards P. falciparum strains K1 and NF 54. The algicolous fungus Phoma tropica contained the new natural product 5-hydroxyramulosin, and the jellyfish-derived culture of Epicoccum purpurascens was found to produce epicoccamide, an unusual structure containing a tetramic acid moiety.