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Developments in Carbohydrate-Based Metzincin Inhibitors

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 deca...

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Autores principales: Cuffaro, Doretta, Nuti, Elisa, D’Andrea, Felicia, Rossello, Armando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696829/
https://www.ncbi.nlm.nih.gov/pubmed/33182755
http://dx.doi.org/10.3390/ph13110376
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author Cuffaro, Doretta
Nuti, Elisa
D’Andrea, Felicia
Rossello, Armando
author_facet Cuffaro, Doretta
Nuti, Elisa
D’Andrea, Felicia
Rossello, Armando
author_sort Cuffaro, Doretta
collection PubMed
description 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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spelling pubmed-76968292020-11-29 Developments in Carbohydrate-Based Metzincin Inhibitors Cuffaro, Doretta Nuti, Elisa D’Andrea, Felicia Rossello, Armando Pharmaceuticals (Basel) Review 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. MDPI 2020-11-10 /pmc/articles/PMC7696829/ /pubmed/33182755 http://dx.doi.org/10.3390/ph13110376 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Cuffaro, Doretta
Nuti, Elisa
D’Andrea, Felicia
Rossello, Armando
Developments in Carbohydrate-Based Metzincin Inhibitors
title Developments in Carbohydrate-Based Metzincin Inhibitors
title_full Developments in Carbohydrate-Based Metzincin Inhibitors
title_fullStr Developments in Carbohydrate-Based Metzincin Inhibitors
title_full_unstemmed Developments in Carbohydrate-Based Metzincin Inhibitors
title_short Developments in Carbohydrate-Based Metzincin Inhibitors
title_sort developments in carbohydrate-based metzincin inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696829/
https://www.ncbi.nlm.nih.gov/pubmed/33182755
http://dx.doi.org/10.3390/ph13110376
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