Studies of NMR, molecular docking, and molecular dynamics simulation of new promising inhibitors of cruzaine from the parasite Trypanosoma cruzi

  • Renato A. Costa
  • Jorddy N. CruzEmail author
  • Fabiana C. A. Nascimento
  • Sebastião G. Silva
  • Silvana O. Silva
  • Marlice C. Martelli
  • Samira M. L. Carvalho
  • Cleydson B. R. Santos
  • Antonio M. J. C. Neto
  • Davi S. B. Brasil
Original Research


Cruzaine is the major cysteine protease of Trypanosoma cruzi. Cruzaine is involved throughout the parasite’s life cycle in host cells, and is a promising target in the search for new antichagasic agents. Quantum chemical calculations based on density functional theory (DFT B3LYP/cc-pVDZ) were performed to obtain nuclear magnetic resonance data and to optimize the geometry of four dihydrochalcones. The results showed good agreement with the experimental data and were used to suggest the relative stereochemistry of one of the four dihydrochalcones studied. In addition, we evaluated the interaction of cruzaine with these new inhibitors. We used molecular dynamics simulations, free energy calculations, and a per-residue energy decomposition method. It was observed that these molecules are capable of interacting with residues important for enzymatic activity, like Cys25, His161, and Asp160. The ranking of the inhibitors obtained from the binding free energy calculations is in agreement with that experimentally reported. The evaluation of the energy components involved in these calculations demonstrated that the van der Waals term is the major contributor to the drug–receptor stabilizing interactions.


RMN New inhibitors Cruzaine Docking Molecular dynamics 



Jorddy N. Cruz appreciate the support of the Federal University of Pará and the National Council for Scientific and Technological Development (CNPq). Conflict of interest The authors declare that there is no conflict of interest regarding the publication of this paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary Figure S3
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Supplementary information


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Renato A. Costa
    • 1
    • 2
  • Jorddy N. Cruz
    • 3
    Email author
  • Fabiana C. A. Nascimento
    • 2
  • Sebastião G. Silva
    • 2
  • Silvana O. Silva
    • 2
  • Marlice C. Martelli
    • 2
  • Samira M. L. Carvalho
    • 2
  • Cleydson B. R. Santos
    • 4
  • Antonio M. J. C. Neto
    • 3
  • Davi S. B. Brasil
    • 2
  1. 1.Federal Institute of ParáParauapebasBrazil
  2. 2.Post-Graduate Program in ChemistryFederal University of ParáBelémBrazil
  3. 3.Laboratory of Preparation and Computation of NanomaterialsFederal University of ParáBelémBrazil
  4. 4.Laboratory of Modeling and Computational ChemistryFederal University of AmapáMacapáBrazil

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