A new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure-based optimization of the well-known arylsulfonamide scaffold is presented. Mols. show an ethylene linker connecting the sulfonamide group with the P1' arom. portion and a D-proline residue bearing the zinc-binding group. The affinity improvement provided by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding group, which might be a promising lead mol. Notably, a significant selectivity for MMP-8, MMP-12, and MMP-13 was obsd. with respect to MMP-1 and MMP-7.
Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold
Mordini Alessandro
2013
Abstract
A new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure-based optimization of the well-known arylsulfonamide scaffold is presented. Mols. show an ethylene linker connecting the sulfonamide group with the P1' arom. portion and a D-proline residue bearing the zinc-binding group. The affinity improvement provided by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding group, which might be a promising lead mol. Notably, a significant selectivity for MMP-8, MMP-12, and MMP-13 was obsd. with respect to MMP-1 and MMP-7.File in questo prodotto:
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