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Comput Biol Chem. 2019 Jun;80:390-397. doi: 10.1016/j.compbiolchem.2019.04.008. Epub 2019 Apr 29.

Evaluation of potential inhibitors of squalene synthase based on virtual screening and in vitro studies.

Author information

1
Center of Scientific Research, Nanyang Medical College, Nanyang, 473061, China. Electronic address: hhaemail@163.com.
2
School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, 526061, China.
3
Nanyang Institute for Food and Drug Inspection and Testing, Nanyang, 473002, China.
4
Center of Scientific Research, Nanyang Medical College, Nanyang, 473061, China.

Abstract

Squalene synthase (SQS) is a potential target for hyperlipidemia treatment. To identify novel chemical scaffolds of SQS inhibitors, we generated 3D-QSAR pharmacophore models using HypoGen. The best quantitative pharmacophore model, Hypo 1, was selected for virtual screening using two chemical databases, Specs and Traditional Chinese Medicine database (TCM). The best-mapped hit compounds were then subjected to filtering by Lipinski's rule of five and docking studies to refine the hits. Finally, five compounds were selected from the top-ranked hit compounds for SQS inhibitory assay in vitro. Three of these compounds could inhibit SQS in vitro, and should be further evaluated pre-clinically as a treatment for hyperlipidemia.

KEYWORDS:

3D-QSAR; In vitro evaluation; Molecular docking; Squalene synthase inhibitor; Virtual screening

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