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 acetyl-cholinesterase (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.
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Acknowledgments This work was supported by Sunchon National University Research Fund in 2022 (Grant Num ber 2022-0298).
© The Korean Society for Applied Biological Chemistry 2023.
- Acremonium sp. CNQ-049
- Dual-functional reversible inhibitor
- Monoamine oxidase