Determination of the absolute configuration of chaetoviridins and other bioactive azaphilones from the endophytic fungus Chaetomium globosum
- Bioorg Med Chem Lett. 2015 Nov 1;25(21):4719-4723. doi: 10.1016/j.bmcl.2015.08.063.
- 1. Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States; Division of Life Sciences, Korea Polar Research Institute, KIOST, Incheon 406-840, Republic of Korea.
- 2. Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
- 3. Chemistry Department, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
- 4. United States Department of Agriculture, Daniel K. Inouye U.S. Pacific Basin Agricultural Research Center, Hilo, HI 96720, United States.
- 5. Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States. Electronic address: [email protected].
Chemical investigation of an endophytic fungus Chaetomium globosum isolated from leaves of Wikstroemia uva-ursi 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-α)-induced nuclear factor-kappa B (NF-κB). 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 μM. Compounds 4, 5, and 9 also displayed (TNF-α)-induced NF-κB activity with IC50 values in the range of 0.9-5.1 μM.