Guineensine, an Acyl-CoA: Cholesterol Acyltransferase Inhibitor, from the Fruits of Piper longum

Abstract

Bioactivity-guided fractionations for ACAT inhibitor led to the isolation of guineensine from the CHCl₃ extract of Piper longum. Its structure was identified by spectroscopic means (IR, UV, MS and NMR). Guineensine inhibited ACAT activity in a dose-dependent manner with an IC₅₀ value of 3.12 µM.

References

• 1 Heinonen T M. Acyl coenzyme A: cholesterol acyltransferase inhibition: potential atherosclerosis therapy or springboard for other discoveries?.  Expert Opin Investig Drugs. 2002;  11 1519-27
• 2 Steinberg D. Atherosclerosis in perspective: hypercholesterolemia and inflammation as partners in crime.  Nature Med. 2002;  8 1211-7
• 3 Sliskovic D R, Picard J A, Krause B R. ACAT inhibitors: The search for a novel and effective treatment of hypercholesterolemia and atherosclerosis.  Prog Med Chem. 2002;  39 121-71
• 4 Doshi R, Wu J, Fishelevich R, Rodriguez A. Update on the role of acyl-CoA: cholesterol acyltransferase inhibitors in atherosclerosis.  Expert Opin Ther Patents. 2001;  11 1655-62
• 5 Jung B S, Shin M K. Piperaceae.  In: Encyclopedia of illustrated Korean natural drugs. Kwon SB, editor Seoul; Young Lim Sa 1998: pp 817-9
• 6 Koul S K, Taneja S C, Agarwal V K, Dhar K L. Minor amides of Piper species.  Phytochemistry. 1988;  27 3523-7
• 7 Banerji A, Banerji J, Chatterjee A. Structure and stereochemistry of an alkamide from Piper sylvaticum .  Indian J Chemistry. 1980;  19B 346-9
• 8 Kwon O E, Rho M C, Song H Y, Lee S W, Chung M Y, Lee J H. et al . Phenylpyropenes A and B, new inhibitors of acyl-CoA: cholesterol acyltransferase produced by Penicillium griseofulvum F1959.  J Antibiotics. 2002;  55 1004-8
• 9 Shoji N, Umeyama A, Saito N, Takemoto T, Kajiwara A, Ohizumi Y. Dehydropipernonaline, an amide possessing coronary vasodilating activity, isolated from Piper longum L.  J Pharm Sci. 1986;  75 1188-9
• 10 Lee S U, Mahoney N E, Campbell B C. Inhibition of aflatoxin B₁ biosynthesis by piperlongumine isolated from Piper longum L.  J Microbiol Biotechnol. 2002;  12 679-82
• 11 Song H Y, Rho M C, Lee S W, Kwon O E, Chang Y D, Lee H S. et al . Isolation of acyl-CoA: cholesterol acyltransferase inhibitor from Persicaria vulgaris .  Planta Med. 2002;  68 845-7