2. Academic Validation
  3. Nevadensin is a naturally occurring selective inhibitor of human carboxylesterase 1

Nevadensin is a naturally occurring selective inhibitor of human carboxylesterase 1

  • Int J Biol Macromol. 2018 Dec;120(Pt B):1944-1954. doi: 10.1016/j.ijbiomac.2018.09.178.
Ya-Qiao Wang 1,  Zi-Miao Weng 2,  Tong-Yi Dou 3,  Jie Hou 4,  Dan-Dan Wang 5,  Le-Le Ding 5,  Li-Wei Zou 5,  Yang Yu 5,  Jing Chen 4,  Hui Tang 6,  Guang-Bo Ge 7
Affiliations

Affiliations

  • 1 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Pharmacy School of Shihezi University, Xinjiang 832000, China.
  • 2 Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Dalian Medical University, Dalian 116044, China.
  • 3 Dalian University of Technology, Dalian 116024, China.
  • 4 Dalian Medical University, Dalian 116044, China.
  • 5 Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 6 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Pharmacy School of Shihezi University, Xinjiang 832000, China. Electronic address: Th_pha@shzu.edu.cn.
  • 7 Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: geguangbo@dicp.ac.cn.
PMID: 30268757 DOI: 10.1016/j.ijbiomac.2018.09.178
Abstract

Human Carboxylesterase 1 (hCE1) is a key Enzyme responsible for the hydrolysis of a wide range of endogenous and xenobiotic esters, but the highly selective inhibitors against hCE1 are rarely reported. This study aimed to assess the inhibitory effects of natural Flavonoids against hCE1 and to find potential specific hCE1 inhibitors. To this end, fifty-eight natural Flavonoids were collected and their inhibitory effects against both hCE1 and hCE2 were assayed. Among all tested compounds, nevadensin, an abundant natural constitute from Lysionotus pauciflorus Maxim., displayed the best combination of inhibition potency and selectivity towards hCE1. The inhibition mechanism of nevadensin on hCE1 was further investigated using two site-specific hCE1 substrates including D-luciferin methyl ester (DME) and 2‑(2‑benzoyloxy‑3‑methoxyphenyl)benzothiazole (BMBT). Furthermore, docking simulations demonstrated that the binding area of nevadensin on hCE1 was highly overlapped with that of DME but was far away from that of BMBT, which was highly consistent with the inhibition modes of nevadensin. These findings found a natural occurring specific inhibitor of hCE1, which could be served as a lead compound for the development of novel hCE1 inhibitor with improved properties, and also hold great promise for investigating hCE1-ligand interactions.

Keywords

Flavonoids; Human carboxylesterase 1 (hCE1); Inhibition mechanism; Nevadensin.

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