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Medicinal Chemistry
ISSN (Print): 1573-4064
ISSN (Online): 1875-6638
Epub Full Text Article
DOI: 10.2174/1573406410666140428152436      Price:  $95

Virtual Screening for Cholesterol Absorption Inhibitors

Author(s): Lidan Sun, Hai Qian and Wenlong Huang
Background: Cholesterol 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. Cholesterol is derived from two different sources of endogenous synthesis and diet. Statins can reduce endogenous sterol synthesis by inhibit HMG-CoA reductase, whereas cholesterol absorption inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by block Niemann-Pick C1-like 1 (NPC1L1).

Objective: The present review focus 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 keep activity in azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone also shows similar activity as ezetimibe. Virtual screening in data bases as computer-aided molecular design tools to propose novel cholesterol absorption inhibitors are kind of complement to design and synthesize structurally novel compounds

Cholesterol absorption inhibitors, ezetimibe, NPC1L1, virtual screening
Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China