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.
Sakai
K
K
Research Laboratories, Tokyo Tanabe Co. Ltd., Japan.
Watanabe
K
K
Masuda
K
K
Tsuji
M
M
Hasumi
K
K
Endo
A
A
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D003169:Complement Inactivator Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013191:Stachybotrys; D002787:Sterol Esterase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001572:Benzofurans; D003169:Complement Inactivator Proteins; C093435:K 76 terpene; D012717:Sesquiterpenes; D013141:Spiro Compounds; C094818:stachybotrydial; D002784:Cholesterol; D002787:Sterol Esterase