Eleven simple alpha-sulfonylphosphonates, new analogues of previously reported alpha-sulfonylaminophosphonates, were prepared and tested as MMP inhibitors. The IC(50) values of most of these compounds are in the nanomolar range against MMP-2, -8, -13, and -14. Compound 11 proved to be the most effective inhibitor of MMP-2 (IC(50) = 60 nM), with interesting selectivity versus the antitarget enzymes MMP-3 and MMP-9. The mode of binding of the new phosphonates in the active site of MMP-2 was studied, and variations in inhibition was explained by means of molecular modeling.
Synthesis, SAR, and Biological Evaluation of alpha-Sulfonylphosphonic Acids as Selective Matrix Metalloproteinase Inhibitors
FRACCHIOLLA, GIUSEPPE;LAGHEZZA, ANTONIO;LOIODICE, Fulvio;TORTORELLA, Paolo
2009-01-01
Abstract
Eleven simple alpha-sulfonylphosphonates, new analogues of previously reported alpha-sulfonylaminophosphonates, were prepared and tested as MMP inhibitors. The IC(50) values of most of these compounds are in the nanomolar range against MMP-2, -8, -13, and -14. Compound 11 proved to be the most effective inhibitor of MMP-2 (IC(50) = 60 nM), with interesting selectivity versus the antitarget enzymes MMP-3 and MMP-9. The mode of binding of the new phosphonates in the active site of MMP-2 was studied, and variations in inhibition was explained by means of molecular modeling.File in questo prodotto:
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