Pharmacophoric modeling and atom-based 3D-QSAR of novel 1-aryl-3-(1-acylpiperidin-4-yl) urea as human soluble epoxide hydrolase inhibitors (sEHIs).
Soluble Epoxide Hydrolase (sEH) is an important and promising new pharmacologic target for the treatment of acute systemic inflammation. Inhibition of sEH by a highly selective and potent sEH inhibitor (sEHI) elevates the epoxyeicosatrienoic acids (EETs) level in vivo leading to decreased inflammation. To explore the necessary structural requirement of 1, 3-disubstituted ureas as sEH inhibitors for anti-inflammatory activity, the molecular modeling studies have been pursued. A ligand-based pharmacophoric model and atom-based 3D-QSAR have been generated by Phase. Binding interaction as determined by the docking study revealed that these inhibitors interact at active site (ASP 335 & TYR 383) of sEH enzyme. The pharmacophore model was further used as a 3D query for virtual screening to retrieve potential inhibitors.
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi- 221 005, India.
Nirupam
N
Das
Meenakshi
M
Dhanawat
Akanksha
A
Kulshrestha
Sushant K
SK
Shrivastava
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014508:Urea; D004851:Epoxide Hydrolases