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Flavonoids as human carboxylesterase 2 inhibitors: Inhibition potentials and molecular docking simulations

Author:
Song, Sha-Sha, Sun, Cheng-Peng, Zhou, Jun-Jun, Chu, Liang
Source:
International journal of biological macromolecules 2019 v.131 pp. 201-208
ISSN:
0141-8130
Subject:
carboxylesterase, computer simulation, humans, inhibitory concentration 50, luteolin
Abstract:
In our search for natural human carboxylesterase 2 (hCE 2) inhibitors from natural products, we investigated inhibitory effects and mechanisms of flavonoids (1–16) against hCE 2. The results demonstrated that kurarinone (1), baicalein (2), 2-[(2′-(1-hydroxy-1-methylethyl)-7′-(3-methyl-2-butenyl)-2′,3′-dihydrobenzofuran)-5-yl]-7-hydroxy-8-(3-methyl-2-butenyl)chroman-4-one (5), luteolin (6), kushenol X (9), and kushenol C (11) displayed significantly inhibitory effects against hCE 2 with IC50 values of 1.46 ± 0.43, 5.22 ± 0.89, 1.13 ± 0.19, 9.78 ± 0.98, 3.05 ± 0.46, and 2.61 ± 0.52 μM, respectively. Compounds 1, 5, 6, 9, and 11 were all uncompetitive inhibitors with Ki values of 1.73, 1.59, 16.89, 1.72, and 0.79 μM, respectively, and their Km values ranged from 2.08 μM to 5.41 μM. Furthermore, molecular docking was conducted for investigating mechanisms of compounds 1, 5, 6, 9, and 11 with hCE 2. These results suggested that compounds 1, 5, 6, 9, and 11 could be served as lead compounds for the development of novel hCE 2 inhibitors.
Agid:
6335947