Inhibitory Activity of Quaternary Isoquinoline Alkaloids on Soluble Epoxide Hydrolase

Abstract

The quaternary isoquinoline alkaloids of palmatine (1), berberine (2), and jatrorrhizine (3) were evaluated in terms of their ability to inhibit soluble epoxide hydrolase (sEH). They had similar inhibitory activities, with IC50 values of 29.6 ± 0.5, 33.4 ± 0.8, and 27.3 ± 0.4 μM, respectively. Their respective Ki values of 26.9, 46.8, and 44.5 μM—determined by enzyme kinetics—indicated that they inhibited the catalytic reaction by binding noncompetitively with sEH. The application of computational chemistry to the in vitro results revealed the site of the receptor to which the ligand would likely bind. Accordingly, three alkaloids were identified as having a suitable basic skeleton for lead compound development of sEH inhibitors.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells

“…Compounds derived from medicinal plants and exhibiting inhibitory activity against sEH have received considerable attention because of their potential therapeutic applications. These compounds primarily include natural flavonoids, terpenoids, alkaloids, anthraquinones, stilbenes, and phenolics [6,[22][23][24][25][26]. Flavonoids are a class of polyphenolic compounds found abundantly in fruits, vegetables, and medicinal plants.…”

New Sight: Enzymes as Targets for Drug Development

“…In the broader context of drug discovery, the spotlight is cast on the vital role played by enzyme kinetics in bridging the gap between enzymology and therapeutic intervention. In this Special Issue, the work of Kim et al presents a captivating exploration of the inhibitory capabilities of quaternary isoquinoline alkaloids against Soluble Epoxide Hydrolase (sEH) [ 3 ]. Through meticulous analyses of enzyme kinetics, a noncompetitive inhibition pattern is unveiled, laying the groundwork for potential therapeutic strategies.…”