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Flavonoids as Strong Inhibitors of MAPK3: A Computational Drug Discovery Approach

Amir Taherkhani1, Parita Khodadadi2, Lida Samie2

  • 1Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

International Journal of Analytical Chemistry
|April 24, 2023
PubMed
Abstract

Insights

This study identified four natural flavonoids—kaempferol 3-rutinoside-4'-glucoside, kaempferol 3-rutinoside-7-sophoroside, rutin, and vicenin-2—as potential inhibitors of mitogen-activated protein kinase 3 (MAPK3). These compounds show promise for developing new cancer therapies by targeting MAPK3 activity.

Area of Science:

  • Computational chemistry
  • Drug discovery
  • Molecular biology

Background:

  • Mitogen-activated protein kinase 3 (MAPK3) is implicated in the development and progression of numerous cancers.
  • Targeting MAPK3 is a potential therapeutic strategy for various malignancies.
  • Previous research demonstrated that inhibiting MAPK3 expression via miRNAs can yield therapeutic benefits in cancer treatment.

Purpose of the Study:

  • To identify natural flavonoid compounds that can inhibit MAPK3 activity.
  • To explore the potential of these flavonoids as novel anti-cancer drug candidates.
  • To computationally evaluate the binding affinity and stability of flavonoids with the MAPK3 catalytic domain.

Main Methods:

  • Computational drug discovery approach utilizing AutoDock and Schrödinger Maestro for molecular docking.
  • Cross-validation of docking results.
  • Molecular dynamics (MD) simulations for 100 ns to assess the stability of docked poses.
  • Analysis of molecular interactions using BIOVIA Discovery Studio Visualizer.

Main Results:

  • Four flavonoids—kaempferol 3-rutinoside-4 -glucoside, kaempferol 3-rutinoside-7-sophoroside, rutin, and vicenin-2—showed significant binding affinity to the MAPK3 active site.
  • The docked poses of these top-ranked compounds remained stable during MD simulations (approximately 45 ns).
  • Detailed analysis revealed strong interactions between these flavonoids and key residues in the MAPK3 active site.

Conclusions:

  • Kaempferol 3-rutinoside-4 -glucoside, kaempferol 3-rutinoside-7-sophoroside, rutin, and vicenin-2 are identified as potent MAPK3 inhibitors.
  • These flavonoids represent promising candidates for the development of novel cancer therapeutics.
  • Further experimental validation is required to confirm their efficacy in cancer treatment.

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