Design, synthesis and biological evaluation of novel benzocoumarin derivatives as potent inhibitors of MAO-B activity

  • Bioorg Med Chem Lett. 2024 Nov 15:113:129984. doi: 10.1016/j.bmcl.2024.129984.
Furkan Meletli  1 ,  Cihan Gündüz  2 ,  Mustafa Muhlis Alparslan  3 ,  Azade Attar  4 ,  Serap Demir  5 ,  Ece İskit  5 ,  Özkan Danış  6
Affiliations
  • 1. Department of Chemistry, Faculty of Science, Marmara University, Istanbul, Turkey. Electronic address: [email protected].
  • 2. Department of Chemistry and Biochemistry, Pace University, New York, USA.
  • 3. Department of Medical Biochemistry, Faculty of Medicine, Biruni University, Istanbul, Turkey.
  • 4. Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yıldız Technical University, Istanbul, Turkey.
  • 5. Department of Chemistry, Faculty of Science, Marmara University, Istanbul, Turkey.
  • 6. Department of Chemistry, Faculty of Science, Marmara University, Istanbul, Turkey. Electronic address: [email protected].
PMID: 39384075 DOI: 10.1016/j.bmcl.2024.129984
Abstract

The continued research of novel reversible inhibitors targeting Monoamine Oxidase (MAO) B remains crucial for effectively symptomatic treatment of Parkinson's disease. In this study we synthesized and evaluated a new series of 3-aryl benzo[g] and benzo[h] coumarin derivatives as MAO-B inhibitors. Compound A6 has been found to display the most potent inhibitory activity and selectivity against the MAO-B isoform (IC50 = 13 nM and SI = >7693.31 respectively). Inhibition mode of A6 on MAO-B was predicted as mixed reversible inhibition with a Ki value of 3.274 nM. Furthermore, in order to elaborate structure-activity relationships, the binding mode of A6 was investigated by molecular docking simulations.

Keywords
Benzo[g]coumarin; Benzo[h]coumarin; Molecular docking; Monoamine oxidase; Parkinson’s Disease.
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