|YOUN, UI JOUNG - University Of Hawaii|
|SRIPISUT, TAWANUN - University Of Hawaii|
|PARK, EUN-JUNG - University Of Hawaii|
|KONDRATYUK, TAMARA - University Of Hawaii|
|FATIMA, NIGHAT - University Of Hawaii|
|SIMMONS, CHARLES - University Of Hawaii|
|SUN, DIANQING - University Of Hawaii|
|PEZZUTO, JOHN - University Of Hawaii|
|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.