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

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 mu M. However, the most potent inhibitor of NPP3 was found as 1x with an IC50 value of 0.214 +/- 0.012 mu M. In addition, compound 1e was the most active inhibitor of NPP2 with an IC50 value of 0.659 +/- 0.007 mu M. Docking studies of the most potent compounds were carried out, and the computational results supported the in vitro results.