Design, Synthesis and Biological Evaluation of Some 2-Azetidinone Derivatives as Potential Antihyperlipidemic Agents

In an effort to develop new molecules with improved antihyperlipidemic activity, eight new 2‐azetidinone analogs (4a–4h) of ezetimibe were designed through in silico docking experiments with the crystal structure of the Niemann‐Pick C1‐like 1 protein (NPC1L1). Synthesis and further antihyperlipdemic...

Full description

Saved in:
Bibliographic Details
Published in:Archiv der Pharmazie (Weinheim) 2013-12, Vol.346 (12), p.872-881
Main Authors: Arya, Nikhilesh, Dwivedi, Jaya, Khedkar, Vijay M., Coutinho, Evans C., Jain, Kishor S.
Format: Article
Language:English
Subjects:
2-Azetidinone
Animals
Antihyperlipidemic
Azetidines - chemical synthesis
Azetidines - metabolism
Azetidines - pharmacology
Binding Sites
Biomarkers - blood
Crystal structure
Crystallography, X-Ray
Disease Models, Animal
Drug Design
Ezetimibe
Female
Hyperlipidemias - blood
Hyperlipidemias - chemically induced
Hyperlipidemias - drug therapy
Hypolipidemic Agents - chemical synthesis
Hypolipidemic Agents - metabolism
Hypolipidemic Agents - pharmacology
Lipids - blood
Male
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Models, Molecular
Molecular docking
Molecular Docking Simulation
Molecular Structure
NPC1L1
Polyethylene Glycols
Protein Conformation
Rats
Rats, Wistar
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In an effort to develop new molecules with improved antihyperlipidemic activity, eight new 2‐azetidinone analogs (4a–4h) of ezetimibe were designed through in silico docking experiments with the crystal structure of the Niemann‐Pick C1‐like 1 protein (NPC1L1). Synthesis and further antihyperlipdemic evaluation of this series in the Triton WR 1339 induced hyperlipidemic rat model showed some of the molecules to exhibit significant lipid‐lowering effects comparable to ezetimibe. Correlation between the observed biological activity and the in silico molecular docking scores of the compounds was observed. To develop new molecules with improved antihyperlipidemic activity, new 2‐azetidinone analogs (4a–4h) of ezetimibe were designed through in silico docking experiments with the crystal structure of the Niemann‐Pick C1‐like 1 protein (NPC1L1). Some of the molecules exhibited significant lipid lowering effects comparable to ezetimibe.
ISSN:0365-6233
1521-4184
DOI:10.1002/ardp.201300262