Novel derivatives of monascus pigment having a high CETP inhibitory activity

Abstract

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 (K_i) values of 2.7 and 4.3 μM, respectively.

Keywords::

• monascus pigment derivatives
• cholesteryl ester transfer protein (CETP)
• inhibitory kinetics

Acknowledgements

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MOE) [No. 2013R1A1A2064267].