title: Design, synthesis and biological evaluation of some 2-azetidinone derivatives as potential antihyperlipidemic agents.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Pune, India; Department of Chemistry, Banasthali University, Tonk, India.
authors.forename: Nikhilesh
authors.initials: N
authors.lastname: Arya
authors.forename: Jaya
authors.initials: J
authors.lastname: Dwivedi
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Khedkar
authors.forename: Evans C
authors.initials: EC
authors.lastname: Coutinho
authors.forename: Kishor S
authors.initials: KS
authors.lastname: Jain
mesh_terms: D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D015415:Biomarkers / Q000097:blood; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D015195:Drug Design; D000069438:Ezetimibe; D005260:Female; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011092:Polyethylene Glycols; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar
chemical_list: C116379:2-azetidinone; D001384:Azetidines; D015415:Biomarkers; D000960:Hypolipidemic Agents; D008055:Lipids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D011092:Polyethylene Glycols; D000069438:Ezetimibe; C016811:tyloxapol
keywords: 2-Azetidinone; Antihyperlipidemic; Ezetimibe; Molecular docking; NPC1L1