Inhibitory Activity of Quaternary Isoquinoline Alkaloids on Soluble Epoxide Hydrolase

Jang Hoon Kim; Chong Woon Cho; Mok Hur; Woo Tae Park; Youn-Ho Moon; Sung-Cheol Koo; Yun-Chan Hur; Jong Seong Kang; Ik Soo Lee

doi:10.3390/cimb44090294

Inhibitory Activity of Quaternary Isoquinoline Alkaloids on Soluble Epoxide Hydrolase

Curr Issues Mol Biol. 2022 Sep 16;44(9):4282-4289. doi: 10.3390/cimb44090294.

Authors

Jang Hoon Kim¹, Chong Woon Cho², Mok Hur¹, Woo Tae Park¹, Youn-Ho Moon¹, Sung-Cheol Koo¹, Yun-Chan Hur¹, Jong Seong Kang², Ik Soo Lee³

Affiliations

¹ Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Korea.
² College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
³ Km Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34134, Korea.

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.

Keywords: molecular simulation; non-competitive inhibitor; quaternary isoquinoline alkaloids; soluble epoxide hydrolase.

Grants and funding

This work was supported by the cooperative research program (PJ01708101) of Rural Development Administration, and the creative challenge research program (NRF-2021R1 L1A1A0105799) of the National Research Foundation of Korea (NRF) funded by Ministry of Education, Republic of Korea.