Novel derivatives of monascus pigment having a high CETP inhibitory activity.
The cholesteryl ester transfer protein (CETP), inhibition of which assists in maintaining a high level of high-density lipoprotein cholesterol in the blood, is a target for anti-atherosclerosis treatments. Orange monascus pigment was produced by a Monascus species in a 5 L jar fermenter and various derivative compounds were synthesised by incorporating 19 different L-amino acids into the orange pigment. Among them, the L-Thr and L-Tyr derivatives exhibited high inhibitory activities against the CETP reaction. The inhibitory activities of the L-Thr and L-Tyr derivatives increased in a dose-dependent manner, resulting in IC50 values of 1.0 and 2.3 μM, respectively. When CETP reactions in the presence of the derivatives were performed, the inhibition modes of the L-Thr and L-Tyr derivatives were non-competitive with inhibition constant (Ki) values of 2.7 and 4.3 μM, respectively.
a Department of Biotechnology , College of Life Science and Biotechnology, Yonsei University , Seodaemun-gu , Seoul , South Korea.
Heeyoung
H
Jang
Deokyeong
D
Choe
Chul Soo
CS
Shin
D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D008076:Cholesterol, HDL / Q000097:blood; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000032:analysis; D015394:Molecular Structure; D032741:Monascus / Q000737:chemistry*; D010860:Pigments, Biological / Q000737:chemistry*; D013912:Threonine / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D010860:Pigments, Biological; D013912:Threonine; D014443:Tyrosine
cholesteryl ester transfer protein (CETP); inhibitory kinetics; monascus pigment derivatives