Research

Bioactive Compounds from Fungi

We have several ongoing projects that are exploring fungi, and my lab’s role is largely the isolation and structure elucidation of bioactive lead compounds. Our longest running project is funded by the National Cancer Institute to examine filamentous fungi for anticancer drug leads. Our portion of the larger project is a collaborative effort with Dr. Cedric Pearce and colleagues at Mycosynthetix, who provide cultures of filamentous fungi, and the laboratory of Dr. Brent Stockwell at Columbia University, who evaluate the biological activity of promising leads. Hundreds of fungal cultures are examined each year, and at any one time, more than a dozen cultures are in various stages of dereplication, isolation, and structure elucidation. To date, we have isolated over 100 anticancer lead compounds, with over 33% of these new to the literature. Moreover, even with the known compounds, over 40% of them have not been evaluated previously for anticancer activity.

We also have two related projects funded by the North Carolina Biotechnology Center. One of these is a logical extension of the project described above, wherein we are again collaborating with Mycosynthetix to examine filamentous fungi for antiparasitic leads, particularly for those parasites that affect livestock and companion animals. In the other project, we are examining endophytes in medicinal herbs. This is a collaborative effort with two colleagues at UNCG, Dr. Nadja Cech and Dr. Stan Faeth.

fungidiagram

Selected Publications:

“Cytotoxic Xanthone-Anthraquinone Heterodimers from an Unidentified Fungus of the Order Hypocreales (MSX 17022).”
Sloan Ayers, Tyler N. Graf, Audrey F. Adcock, David J. Kroll, Qi Shen, Steven M. Swanson, Susan Matthew, Esperanza J. Carcache de Blanco, Mansukh C. Wani, Blaise A. Darveaux, Cedric J. Pearce, and Nicholas H. Oberlies
Journal of Antibiotics, 2012, 65, 3-8.
PMID: 22068158; doi: 10.1038/ja.2011.95

“Thielavin B Methyl Ester: A Cytotoxic Benzoate Trimer from an Unidentified Fungus (MSX 55526) from the Order Sordariales.”
Sloan Ayers, Brandie M. Ehrmann, Audrey F. Adcock, David J. Kroll, Mansukh C. Wani, Cedric J. Pearce, and Nicholas H. Oberlies
Tetrahedron Letters, 2011, 52, 5733-5735. doi: 10.1016/j.tetlet.2011.08.125

“Resorcylic Acid Lactones with Cytotoxic and NF-kB Inhibitory Activities and Their Structure-Activity Relationships.”
Sloan Ayers, Tyler N. Graf, Audrey F. Adcock, David J. Kroll, Susan Matthew, Esperanza J. Carcache de Blanco, Qi Shen, Steven M. Swanson, Mansukh C. Wani, Cedric J. Pearce, and Nicholas H. Oberlies
Journal of Natural Products, 2011, 74, 1126-1131.
PMID:21513293; PMCID: PMC3111092; doi: 10.1021/np200062x

“Obionin B: An O-Pyranonaphthoquinone Decaketide from an Unidentified Fungus (MSX 63619) from the Order Pleosporales.”
Sloan Ayers, Tyler N. Graf, Audrey F. Adcock, David J. Kroll, Qi Shen, Steven M. Swanson, Mansukh C. Wani, Blaise A. Darveaux, Cedric J. Pearce, and Nicholas H. Oberlies
Tetrahedron Letters, 2011, 52, 5128-5230.
PMID:22025810; PMCID: PMC3183506; doi: 10.1016/j.tetlet.2011.07.102

“Cyclodepsipeptides, Sesquiterpenoids, and Other Cytotoxic Metabolites from the Filamentous Fungus Trichothecium sp. (MSX 51320).”
Arlene A. Sy-Cordero, Tyler N. Graf, Audrey F. Adcock, David J. Kroll, Qi Shen, Steven M. Swanson, Mansukh C. Wani, Cedric J. Pearce, and Nicholas H. Oberlies
Journal of Natural Products, 2011, 74, 2137-2142.
PMID:21978324; doi: 10.1021/np2004243

“Dereplication of Macrocyclic Trichothecenes from Extracts of Filamentous Fungi through UV and NMR Profiles.”
Arlene A. Sy-Cordero, Tyler N. Graf, Mansukh C. Wani, David J. Kroll, Cedric J. Pearce, and Nicholas H. Oberlies
Journal of Antibiotics, 2010, 63, 539-544.
PMID:20648023; PMCID: PMC2946446; doi: 10.1038/ja.2010.77