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Discovery of novel cholesteryl ester transfer protein (CETP) inhibitors by a multi-stage virtual screening

Authors :
Yanfeng Liu
Liangying Deng
Feng Ding
Qiang Wang
Shuran Zhang
Nana Mi
Wenhui Zhang
Bailin Zeng
Huangjin Tong
Lixing Wu
Source :
BMC Chemistry, Vol 18, Iss 1, Pp 1-16 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Cholesteryl ester transfer protein (CETP) is a promising therapeutic target for cardiovascular diseases. It effectively lowers the low-density lipoprotein cholesterol levels and increases the high-density lipoprotein cholesterol levels in the human plasma. This study identified novel and highly potent CETP inhibitors using virtual screening techniques. Molecular docking and molecular dynamics (MD) simulations revealed the binding patterns of these inhibitors, with the top 50 compounds selected according to their predicted binding affinity. Protein–ligand interaction analyses were performed, leading to the selection of 26 compounds for further evaluation. A CETP inhibition assay confirmed the inhibitory activities of the selected compounds. The results of the MD simulations revealed the structural stability of the protein–ligand complexes, with the binding site remaining significantly unchanged, indicating that the five compounds (AK-968/40709303, AG-690/11820117, AO-081/41378586, AK-968/12713193, and AN-465/14952302) identified have the potential as active CETP inhibitors and are promising leads for drug development. Graphical Abstract

Details

Language :
English
ISSN :
2661801X
Volume :
18
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMC Chemistry
Publication Type :
Academic Journal
Accession number :
edsdoj.90fb942c79524cd19977b7e84f3fe01a
Document Type :
article
Full Text :
https://doi.org/10.1186/s13065-024-01192-5