Journal of Applied Biological Chemistry

  • Volume 66
  • /
  • Pages.165-170
  • /
  • 2023
  • /
  • 1976-0442(pISSN)
  • /
  • 2234-7941(eISSN)
The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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3-Phenethyl-2-phenylquinazolin-4(3H)-one isolated from marine-derived Acremonium sp. CNQ-049 as a dual- functional inhibitor of monoamine oxidases-B and butyrylcholinesterase

  • Jong Min Oh (Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University) ;
  • Prima F. Hillman (Department of Chemistry and Nanoscience, Ewha Womans University) ;
  • Sang-Jip Nam (Department of Chemistry and Nanoscience, Ewha Womans University) ;
  • Hoon Kim (Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University)
  • Received : 2023.03.15
  • Accepted : 2023.04.14
  • Published : 2023.12.31
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Abstract

Isolation of the culture broth of a marine-derived Acremonium sp. CNQ-049 guided by HPLC-UV yielded compound 1 (3-phenethyl-2-phenylquinazolin-4(3H)-one), and its inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase 1 (BACE1) were evaluated. Compound 1 was an effective selective MAO-B inhibitor with an IC50 value of 9.39 µM and a selectivity index (SI) value of 4.26 versus MAO-A. In addition, compound 1 showed a potent selective butyrylcholinesterase (BChE) inhibition with an IC50 value of 7.99 µM and an SI value of 5.01 versus acetylcholinesterase (AChE). However, compound 1 showed weak inhibitions against MAO-A, AChE, and BACE1. The Ki value of compound 1 for MAO-B was 5.22±1.73 µM with competitive inhibition, and the Ki value of compound 1 for BChE was 3.00±1.81 µM with mixed-type inhibition. Inhibitions of MAO-B and BChE by compound 1 were recovered by dialysis experiments. These results suggest that compound 1 is a dual-functional reversible inhibitor of MAO-B and BChE, that can be used as a treatment agent for neurological disorders.

Keywords

Acknowledgement

This work was supported by Sunchon National University Research Fund in 2022 (Grant Number 2022-0298).

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