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ARS Home » Pacific West Area » Hilo, Hawaii » Daniel K. Inouye U.S. Pacific Basin Agricultural Research Center » Tropical Plant Genetic Resources and Disease Research » Research » Publications at this Location » Publication #313056

Research Project: Molecular Resources for the Improvement of Tropical Ornamental and Fruit Crops

Location: Tropical Plant Genetic Resources and Disease Research

Title: Determination of the absolute configuration of Chaetoviridins and other bioactive Azaphilones from the endophytic fungus Chaetomium globosum

Author
item YOUN, UI JOUNG - University Of Hawaii
item SRIPISUT, TAWANUN - University Of Hawaii
item PARK, EUN-JUNG - University Of Hawaii
item KONDRATYUK, TAMARA - University Of Hawaii
item FATIMA, NIGHAT - University Of Hawaii
item SIMMONS, CHARLES - University Of Hawaii
item Wall, Marisa
item SUN, DIANQING - University Of Hawaii
item PEZZUTO, JOHN - University Of Hawaii
item CHANG, LENG CHEE - University Of Hawaii

Submitted to: Bioorganic and Medicinal Chemistry Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/24/2015
Publication Date: 11/1/2015
Citation: Youn, U., Sripisut, T., Park, E., Kondratyuk, T.P., Fatima, N., Simmons, C.J., Wall, M.M., Sun, D., Pezzuto, J.M., Chang, L. 2015. Determination of the absolute configuration of Chaetoviridins and other bioactive Azaphilones from the endophytic fungus Chaetomium globosum. Bioorganic and Medicinal Chemistry Letters. 25:4719-4723.

Interpretive Summary: Chemical extracts of an endophytic fungus, Chaetomium globosum, found in the Hawaiian native plant Wikstroemia uva-ursi (Akia), demonstrated anti-cancer activity in bioassays. Bioassay-guided fractionation of the extract resulted in the isolation of two new chaetoviridins, together with four known compounds. This paper reports the isolation and chemical structure of the new chaetoviridins and the biological activity of all compounds. Three of the compounds demonstrated cancer chemopreventive potential based on their ability to inhibit tumor necrosis factor alpha (TNF-a)-induced NF-'B activity and nitric oxide (NO) production.

Technical Abstract: Chemical investigation of an endophytic fungus Chaetomium globosum isolated from leaves of Wikstroemia uva-ursi led to the isolation of a new azaphilone, chaetoviridin J (1), and a new stereoisomer, chaetoviridin K (2), along with four known derivatives (3–6). The structures of azaphilones were determined by NMR, Mosher’s method, and CD analysis. The absolute configuration of chaetoviridin K (2) was also determined by chemical transformation and X-ray diffraction analysis. Compounds 3, 4, and 8 inhibited TNF-a-induced NF-'B activity with IC50 values in the range of 0.9-5.1 uM. Compounds 3, 4, and 6–8 also displayed nitric oxide (NO) inhibitory activity with IC50 values in the range of 0.3-5.8 uM.