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Synthesis and evaluation of chromone derivatives as inhibitors of monoamine oxidase

  • Annah N. Mpitimpiti
  • Jacobus P. PetzerEmail author
  • Anél Petzer
  • Johannes H. L. Jordaan
  • Anna C. U. Lourens
Original Article
  • 49 Downloads

Abstract

Based on reports that chromone compounds are good potency inhibitors of monoamine oxidase (MAO), the present study evaluates the effect of substitution with flexible side chains on the 3 position on MAO inhibition potency. Fifteen chromone derivatives were synthesised by reacting aromatic and aliphatic amines and alcohols with chromone 3-carboxylic acid in the presence of carbonyldiimidazole (CDI). This yielded chromane-2,4-dione and ester chromone derivatives. Generally, the esters exhibited weak MAO inhibition, while the chromane-2,4-dione derivatives showed promise as selective MAO-B inhibitors with IC50 values in the micromolar range. Compound 14b, 3-[(benzylamino)methylidene]-3,4-dihydro-2H-1-benzopyran-2,4-dione, was the most potent MAO-B inhibitor with an IC50 value of 638 µM. This compound was shown to be a reversible and competitive MAO-B inhibitor with a Ki of 94 µM. In conclusion, the effect of chain elongation and introduction of flexible substituents on position 3 of chromone were explored and the results showed that aminomethylidene substitution is preferable over ester substitution. Good potency MAO-B inhibitors may act as leads for the design and development of therapy for Parkinson’s disease where these agents reduce the central metabolism of dopamine.

Graphical abstract

Keywords

Chromone Chromandione Monoamine oxidase MAO Inhibitor Competitive Parkinson’s disease 

Notes

Acknowledgements

The NMR and MS spectra were recorded by André Joubert and Johan Jordaan of the Laboratory for Analytical Services (LAS) in the focus area Chemical Resource Beneficiation, while HPLC analysis was carried out by Jan du Preez of the Analytical Technology Laboratory (ATL) at the North-West University (NWU). X-ray crystallography was carried out by Johan Jordaan.

Funding

The financial assistance of the National Research Foundation (NRF) of South Africa [Grant specific unique reference numbers (UID) 85642, 96180, 76308] towards this research is hereby acknowledged. The Grantholders acknowledge that opinions, findings and conclusions or recommendations expressed in any publication generated by the NRF supported research are that of the authors, and that the NRF accepts no liability whatsoever in this regard.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11030_2019_9917_MOESM1_ESM.pdf (3.6 mb)
Table S1 and Fig. S1: 1H NMR, 13C NMR, mass spectra and infra-red spectra for the synthesised compounds (PDF 3671 kb)

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Centre of Excellence for Pharmaceutical SciencesNorth-West UniversityPotchefstroomSouth Africa
  2. 2.Pharmaceutical Chemistry, School of PharmacyNorth-West UniversityPotchefstroomSouth Africa
  3. 3.Research Focus Area for Chemical Resource BeneficiationNorth-West UniversityPotchefstroomSouth Africa

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