New azaphilones and chlorinated phenolic glycosides from Chaetomium elatum with caspase-3 inhibitory activity.
Three new azaphilones, chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3), and two new chlorinated phenolic glycosides, globosumoside A (4) and globosumoside B (5), were isolated from the crude extract of the fungal strain Chaetomium elatum No. 89-1-3-1. Their structures were determined by detailed NMR and MS spectroscopic analyses. The absolute configurations of C-7 in chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3) were assigned by CD experiments, and the absolute configurations of 1 and 2 were established by X-ray crystallography. Compounds 1-3 are the first examples of 7R-configurated azaphilones with a chlorinated isochromen from Chaetomium spp. In addition, compounds 1-3 showed inhibitory activity in the cysteine aspartyl-specific protease-3 (caspase-3) enzymatic assay, with IC₅₀ values of 20.6, 10.9, and 7.9 µM, respectively.
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China.
Guo-Dong
GD
Chen
Yan-Jun
YJ
Li
Hao
H
Gao
Ying
Y
Chen
Xiao-Xia
XX
Li
Jia
J
Li
Liang-Dong
LD
Guo
Ying-Zhou
YZ
Cen
Xin-Sheng
XS
Yao
D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects; D061945:Caspase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002457:Cell Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002597:Chaetomium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054879:Halogenation; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008516:Medicine, Chinese Traditional; D008958:Models, Molecular; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010860:Pigments, Biological / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011994:Recombinant Proteins
D001578:Benzopyrans; D061945:Caspase Inhibitors; D002457:Cell Extracts; D006027:Glycosides; D010636:Phenols; D010860:Pigments, Biological; D011994:Recombinant Proteins; C494154:azaphilone; D053148:Caspase 3