Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Potent Selective Inhibition of Monoamine Oxidase A by Alternariol Monomethyl Ether Isolated from Alternaria brassicae

  • Lee, Hyun Woo (Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University) ;
  • Kim, Yeon Ji (Department of Chemistry and Nano Science, Ewha Womans University) ;
  • Nam, Sang-Jip (Department of Chemistry and Nano Science, Ewha Womans University) ;
  • Kim, Hoon (Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University)
  • Received : 2016.10.21
  • Accepted : 2016.11.04
  • Published : 2017.02.28
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Abstract

Alternariol monomethyl ether (AME), a dibenzopyrone derivative, was isolated from Alternaria brassicae along with altertoxin II (ATX-II). The compounds were tested for the inhibitory activity of monoamine oxidase (MAO), which catalyzes neurotransmitting monoamines. AME was found to be a highly potent and selective inhibitor of human MAO-A with an $IC_{50}$ value of $1.71{\mu}M$; however, it was found to be ineffective for MAO-B inhibition. ATX-II was not effective for the inhibition of either MAO-A or MAO-B. The inhibition of MAO-A using AME was apparently instantaneous. MAO-A activity was almost completely recovered after the dilution of the inhibited enzyme with an excess amount of AME, suggesting AME is a reversible inhibitor. AME showed mixed inhibition for MAO-A in Lineweaver-Burk plots with a $K_i$ value of $0.34{\mu}M$. The findings of this study suggest that microbial metabolites and dibenzopyrone could be potent MAO inhibitors. In addition, AME could be a useful lead compound for developing reversible MAO-A inhibitors to treat depression, Parkinson's disease, and Alzheimer's disease.

Keywords

References

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