2. Academic Validation
  3. Determination of the absolute configuration of chaetoviridins and other bioactive azaphilones from the endophytic fungus Chaetomium globosum

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.
Ui Joung Youn 1,  Tawanun Sripisut 2,  Eun-Jung Park 2,  Tamara P Kondratyuk 2,  Nighat Fatima 2,  Charles J Simmons 3,  Marisa M Wall 4,  Dianqing Sun 2,  John M Pezzuto 2,  Leng Chee Chang 5
Affiliations

Affiliations

  • 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: lengchee@hawaii.edu.
PMID: 26343828 DOI: 10.1016/j.bmcl.2015.08.063
Abstract

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.

Keywords

Anti-inflammatory activity; Azaphilone; Chaetomium globosum; Wikstroemia uva-ursi; X-ray crystallography.

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