Inhibitory Activity of Quaternary Isoquinoline Alkaloids on Soluble Epoxide Hydrolase

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...

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Published in:Current issues in molecular biology 2022-09, Vol.44 (9), p.4282-4289
Main Authors: Kim, Jang Hoon, Cho, Chong Woon, Hur, Mok, Park, Woo Tae, Moon, Youn-Ho, Koo, Sung-Cheol, Hur, Yun-Chan, Kang, Jong Seong, Lee, Ik Soo
Format: Article
Language:English
Subjects:
molecular simulation
non-competitive inhibitor
quaternary isoquinoline alkaloids
soluble epoxide hydrolase
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Summary: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.
ISSN:1467-3045
1467-3037
1467-3045
DOI:10.3390/cimb44090294