Synthesis, biological evaluation, and molecular docking study of sulfonate derivatives as nucleotide pyrophosphatase/phosphodiesterase (NPP) inhibitors

Bioorg Med Chem. 2019 Jul 1;27(13):2741-2752. doi: 10.1016/j.bmc.2019.04.031. Epub 2019 Apr 26.

Abstract

A new series of sulfonate derivatives 1a-zk were synthesized and evaluated as inhibitors of nucleotide pyrophosphatases. Most of the compounds exhibited good to moderate inhibition towards NPP1, NPP2, and NPP3 isozymes. Compound 1m was a potent and selective inhibitor of NPP1 with an IC50 value of 0.387 ± 0.007 µM. However, the most potent inhibitor of NPP3 was found as 1x with an IC50 value of 0.214 ± 0.012 µM. In addition, compound 1e was the most active inhibitor of NPP2 with an IC50 value of 0.659 ± 0.007 µM. Docking studies of the most potent compounds were carried out, and the computational results supported the in vitro results.

Keywords: Homology modeling; Immune modulation; Molecular docking; Nucleotide pyrophosphatase; Sulfonate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Docking Simulation / methods*
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Pyrophosphatases / metabolism
  • Pyrophosphatases / pharmacology
  • Pyrophosphatases / therapeutic use*
  • Structure-Activity Relationship

Substances

  • Phosphodiesterase Inhibitors
  • Pyrophosphatases
  • nucleotide pyrophosphatase

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