A novel compound 1 and nine known compounds (2–10) were isolated by open column chromatography analysis of the root bark Ulmus davidiana. Pure (1–10) tested in vitro to determine inhibitory activity catalytic reaction soluble epoxide hydrolase (sEH). Compounds 1, 2, 4, 6–8, 10 had IC50 values ranging from 11.4 ± 2.3 36.9 2.6 μM. We used molecular docking simulate inhibitor binding each estimate...

Inhibition of xenobiotic-metabolizing enzymes by metals may represent an important mechanism in regulating enzyme activity. Fourteen cations were evaluated for inhibition of microsomal epoxide hydrolase (mEH) (mouse, rat, and human liver), soluble epoxide hydrolase (sEH) (mouse, rat, and human liver), and recombinant potato sEH. Of the metals tested, Hg2+ and Zn2+ were the strongest inhibitors ...

Quantum chemical studies of enzymatic reactions are able to provide detailed insight into mechanisms and catalytic strategies. The energetic feasibility of proposed mechanisms can be established, and new possible reaction pathways can be put forward. The role of the involved active site residues can be analyzed in detail and the origins for experimentally observed selectivities can be investiga...

Introduction Promotion and improvement of cardiopulmonary resuscitation (CPR) technique contributes to increase of the survivors from unexpected cardiac arrest (CA). However, many patients have some neurological deficits, because of few effective treatment to improve the outcome. Hippocampus damage causes a memory dysfunction which suffers the survivors. Microglia activation caused neuron damag...

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea groups has been developed. Inhibition potency of the described compounds ranges from 2.0 μM to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl)urea] (3b) was found to be a potent slow tight binding inhibitor (IC50=0.5 nM) with a strong binding to sEH (Ki=3.1 nM) and a moderately long residence time on the enzyme (kof...

A 192-member library of N,N'-disubstituted urea inhibitors was synthesized by a solid-phase method. The ureas were tested for their inhibitory activities against recombinant human soluble epoxide hydrolase. Simple carbocyclic or para/meta-substituted phenyl groups showed inhibition potencies that were equal to or greater than adamantane-based sEH inhibitors, while the presence of bulky or ioniz...

Inhibition of soluble epoxide hydrolase (sEH) has been proposed as a new pharmaceutical approach for treating hypertension and vascular inflammation. The most potent sEH inhibitors reported in literature to date are urea derivatives. However, these compounds have limited pharmacokinetic profiles. We investigated non-urea amide derivatives as sEH inhibitors and identified a potent human sEH inhi...

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the constr...