Isolation, characterization and biological activities of novel triprenyl phenols as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F-1839.

Ten triprenyl phenol metabolites were isolated as inhibitors of pancreatic cholesterol esterase from cultures of Stachybotrys sp. F-1839 by solvent extraction and column chromatographies. Combination of spectroscopic analyses revealed that two of these compounds are K-76 (1) and stachybotrydial (2), and that the remaining eight are new congeners (designated F1839-A (3), -B (4), -C (5), -D (6), -E (7), -F (8), -I (9) and -J (10). These compounds inhibited pancreatic cholesterol esterase by 50% at 6 x 10(-5) to 1.1 x 10(-1) M. Inhibition of the enzyme by compound 2, the most potent one among these compounds, was time-dependent and irreversible. When administered to normal rats, 2, at a single oral dose of 100 mg/kg, reduced [14C]cholesterol absorption by 50-60%. In cholesterol-fed mice, dietary supplementation of 2 (0.1%) for 14 days resulted in a 20% reduction in serum total cholesterol level without causing significant change in the high density lipoprotein cholesterol level.