Investigation of inhibitory potential of quercetin to the pyruvate dehydrogenase kinase 3: Towards implications in anticancer therapy

Rashmi Dahiya, Taj Mohammad, Sonam Roy, Saleha Anwar, Preeti Gupta, Anzarul Haque, Parvez Khan, Syed Naqui Kazim, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Pyruvate dehydrogenase kinase 3 (PDK3) is a mitochondrial protein, has recently been considered as a potential pharmacological target for varying types of cancer. Here, we report the binding mechanism of quercetin to the PDK3 by using molecular docking, simulation, fluorescence spectroscopy and isothermal titration calorimetric assays. Molecular docking along with simulation provided an in-depth analysis of protein-ligand interactions. We have observed that quercetin interacts to the important residues of active site cavity of PDK3 and shows a well-ordered conformational fitting. The stability of quercetin-PDK3 complex is maintained by several non-covalent interactions throughout the simulation. To complement in silico findings with the experiments, we have successfully expressed and purified human PDK3. Both fluorescence and isothermal titration calorimetric experiments showed excellent binding affinity of quercetin to the PDK3. Kinase inhibition assay further revealed a significant inhibitory potential of quercetin to the PDK3 with the IC50 values in μM range. Quercetin is non-toxic to HEK293, and significantly inhibits the proliferation of cancer (HepG2 and A549) cell lines. All these observations clearly indicate that quercetin may be further evaluated as promising therapeutic molecule for PDK3 with required modifications and in vivo validation.

Original languageEnglish (US)
Pages (from-to)1076-1085
Number of pages10
JournalInternational Journal of Biological Macromolecules
StatePublished - Sep 1 2019
Externally publishedYes


  • Enzyme inhibition
  • Kinase inhibitors
  • MD simulation
  • Molecular docking
  • PDK3 inhibitor
  • Pyruvate dehydrogenase kinase
  • Quercetin

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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