Developments in Carbohydrate-Based Metzincin Inhibitors.

Published on Nov 10, 2020in Pharmaceuticals4.286
· DOI :10.3390/PH13110376
Doretta Cuffaro5
Estimated H-index: 5
(UniPi: University of Pisa),
Elisa Nuti25
Estimated H-index: 25
(UniPi: University of Pisa)
+ 1 AuthorsArmando Rossello28
Estimated H-index: 28
(UniPi: University of Pisa)
Matrix metalloproteinases (MMPs) and A disintegrin and Metalloproteinase (ADAMs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. Upregulation of metzincin activity is a major feature in many serious pathologies such as cancer, inflammations, and infections. In the last decades, many classes of small molecules have been developed directed to inhibit these enzymes. The principal shortcomings that have hindered clinical development of metzincin inhibitors are low selectivity for the target enzyme, poor water solubility, and long-term toxicity. Over the last 15 years, a novel approach to improve solubility and bioavailability of metzincin inhibitors has been the synthesis of carbohydrate-based compounds. This strategy consists of linking a hydrophilic sugar moiety to an aromatic lipophilic scaffold. This review aims to describe the development of sugar-based and azasugar-based derivatives as metzincin inhibitors and their activity in several pathological models.
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