Insights into the Complex Formed by Matrix Metalloproteinase-2 and Alloxan Inhibitors: Molecular Dynamics Simulations and Free Energy Calculations
2011

Study of Alloxan Inhibitors for Matrix Metalloproteinase-2

publication Evidence: moderate

Author Information

Author(s): Giangreco Ilenia, Lattanzi Gianluca, Nicolotti Orazio, Catto Marco, Laghezza Antonio, Leonetti Francesco, Stefanachi Angela, Carotti Angelo

Primary Institution: University of Bari “Aldo Moro”

Hypothesis

Can alloxan-based compounds be effectively modified to inhibit MMP-2?

Conclusion

The study found that modified alloxan compounds can effectively inhibit MMP-2 with high affinity and selectivity.

Supporting Evidence

  • The alloxan core was identified as a novel zinc-binding group for MMP-2.
  • Molecular dynamics simulations showed that the ligand remains stable in the binding pocket.
  • The highest affinity compound, BAM, exhibited a pIC50 of 7.06.
  • BAM showed over 20-fold selectivity towards MMP-2 compared to MMP-9.

Takeaway

Scientists created new drugs from alloxan that can stop a specific enzyme related to cancer, making them potentially useful for treatment.

Methodology

The study used molecular dynamics simulations and free energy calculations to analyze the binding of alloxan derivatives to MMP-2.

Limitations

The study may have limitations in sampling protein conformations during simulations.

Digital Object Identifier (DOI)

10.1371/journal.pone.0025597

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