Evaluation of potential inhibitors of squalene synthase based on virtual screening and in vitro studies.
Comput Biol Chem
; 80: 390-397, 2019 Jun.
Article
in En
| MEDLINE
| ID: mdl-31125877
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Farnesyl-Diphosphate Farnesyltransferase
/
Enzyme Inhibitors
Type of study:
Diagnostic_studies
/
Screening_studies
Language:
En
Journal:
Comput Biol Chem
Journal subject:
BIOLOGIA
/
INFORMATICA MEDICA
/
QUIMICA
Year:
2019
Document type:
Article