Abstract:
:Continuous efforts to identify sEH inhibitors using activity-guided fractionation have revealed 12 known compounds, 2-13, from Rheum undulatum. Compounds 2-13 and 1, which was obtained from the in-house library, were tested for inhibitory activity against sEH. Compounds 1-9, 11, and 12 were shown to have inhibitory activity, with IC50 values ranging from 2.5 ± 0.5 to 53.2 ± 4.4 μM. They were subjected to enzyme kinetic studies to explore the binding mode between the ligand and receptor. Based on our results, compounds 1, 2, 5-9, and 11 (mixed type) and compounds 3 and 12 (noncompetitive type) had a preferred allosteric site. Compound 4 was identified as a competitive-type interaction in the active site. Molecular docking studies revealed the interacting residues and binding energy between sEH and inhibitors. Additionally, molecular dynamics provided detailed information on the interaction between the ligand and receptor.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Jo AR,Kim JH,Yan XT,Yang SY,Kim YHdoi
10.1080/14756366.2016.1189421subject
Has Abstractpub_date
2016-01-01 00:00:00pages
70-78issue
sup2eissn
1475-6366issn
1475-6374journal_volume
31pub_type
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