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

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

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Marmara University, Istanbul, Turkey. Electronic address: furkan.meletli@marmara.edu.tr.
  • 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: odanis@marmara.edu.tr.
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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