Determination of the absolute configuration of chaetoviridins and other bioactive azaphilones from the endophytic fungus Chaetomium globosum

Abstract

Chemical investigation of an endophytic fungus <em>Chaetomium globosum</em> isolated from leaves of <em>Wikstroemia uva-ursi</em> led to the isolation of two new azaphilones, chaetoviridins J and K (1 and 3), along with five known derivatives (2 and 4-7). The structures of azaphilones were determined by NMR, X-ray diffraction, Mosher's method, and CD analysis. The isolated compounds were evaluated for their cancer chemopreventive-potential based on their abilities to inhibit tumor necrosis factor alpha (TNF-a)-induced nuclear factor-kappa B (NF-jB). Compounds 4, 5, 7, and synthetic 8 and 9 inhibit nitric oxide (NO) production with IC50 values in the range of 0.3-5.8 lM. Compounds 4, 5, and 9 also displayed (TNF-a)-induced NF-jB activity with IC50 values in the range of 0.9-5.1 lM.