2. Academic Validation
  3. Flavonoids as human carboxylesterase 2 inhibitors: Inhibition potentials and molecular docking simulations

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

  • Int J Biol Macromol. 2019 Jun 15;131:201-208. doi: 10.1016/j.ijbiomac.2019.03.060.
Sha-Sha Song 1,  Cheng-Peng Sun 2,  Jun-Jun Zhou 3,  Liang Chu 4
Affiliations

Affiliations

  • 1 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 2 College of Pharmacy, College (Institute) of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 3 College of Pharmacy, College (Institute) of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian, Liaoning, 116044, China. Electronic address: zhoujun_2005@163.com.
  • 4 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: liangchu@tjh.tjmu.edu.cn.
PMID: 30872054 DOI: 10.1016/j.ijbiomac.2019.03.060
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.

Keywords

Flavonoids; Human carboxylesterase 2; Molecular docking.

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