Fungi are now generally accepted as the largest group of organisms on Earth after insects; as a working figure the Global Biodiversity Assessments accept the estimate that there are 1.5 million species of fungi.1 Approximately 99,000 species have been described so far (only 6.6% of 1.5 million) and of this number only a small portion have been chemically investigated.2 Numerous bioactive compounds, mostly secondary metabolites, have been isolated from fungi and subsequently shown to display antimicrobial, anticancer, antioxidant, anti-inflammatory and other medicinal properties.3 Important drugs, such as the immunosuppressant cyclosporin A, the penicillin class of antibiotics, and the lipid-lowering “statins” were all isolated from fungi.3 Thus the use of these organisms for biodiscovery has a strategic advantage, since this unique and chemically diverse resource has only been superficially explored.
The Davis group has established a biodiscovery project that aims to discover new antimalarial lead compounds from terrestrial micro- and macrofungi. In vitro screening of a fungi-derived prefractionated library recently identified several fractions that inhibited the growth of the malaria parasite Plasmodium falciparum (3D7 line) and also displayed no cytotoxicity against neonatal foreskin fibroblast (NFF) cells.4 Chemistry and biology outcomes from the UV-guided fractionation of one antimalarial fungal extract will be presented along with the synthesis, and antimalarial evaluation of a novel tetrahydroanthraquinone-based library.