Determination of the absolute configuration of chaetoviridins and other bioactive azaphilones from the endophytic fungus Chaetomium globosum.
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.
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.
Ui Joung
UJ
Youn
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
Tawanun
T
Sripisut
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
Eun-Jung
EJ
Park
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
Tamara P
TP
Kondratyuk
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
Nighat
N
Fatima
Chemistry Department, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
Charles J
CJ
Simmons
United States Department of Agriculture, Daniel K. Inouye U.S. Pacific Basin Agricultural Research Center, Hilo, HI 96720, United States.
Marisa M
MM
Wall
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
Dianqing
D
Sun
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI 96720, United States.
John M
JM
Pezzuto
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.
Leng Chee
LC
Chang
D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002597:Chaetomium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001578:Benzopyrans; D006576:Heterocyclic Compounds, 4 or More Rings; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C000608284:chaetoviridin J; C000608285:chaetoviridin K; D009569:Nitric Oxide
Anti-inflammatory activity; Azaphilone; Chaetomium globosum; Wikstroemia uva-ursi; X-ray crystallography