Virtual Screening for Cholesterol Absorption Inhibitors

Title:Virtual Screening for Cholesterol Absorption Inhibitors

Volume: 11 Issue: 1

Author(s): Lidan Sun, Hai Qian and Wenlong Huang

Affiliation:

Keywords: Cholesterol absorption inhibitors, ezetimibe, NPC1L1, virtual screening.

Abstract: Background: Cholesterol, derived from two different sources of endogenous synthesis and diet, is essential for the growth and maintenance of mammalian cells. However, elevated level of serum cholesterol is among the associated risk factors for the coronary heart disease. Statins can reduce endogenous sterol synthesis by inhibiting HMG-CoA reductase, whereas cholesterol absorption inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by blocking Niemann- Pick C1-like 1 (NPC1L1).

Objective: The present review focuses on the main research progress of cholesterol absorption inhibitors, the structure of NPC1L1 and discovery of novel chemical entities by virtual screening.

Conclusion: Studies on the structure-activity relationship reveal that azetidinone is important to maintain activity in azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone also show similar activity as ezetimibe. Moreover, virtual screening is a computer-aided molecular design tool to propose novel cholesterol absorption inhibitors.

Cite this article as:

Sun Lidan, Qian Hai and Huang Wenlong, Virtual Screening for Cholesterol Absorption Inhibitors, Medicinal Chemistry 2015; 11 (1) . https://dx.doi.org/10.2174/1573406410666140428152436