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(2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone

Matrix Metalloproteinases (MMPs) are a family of secreted and membrane-bound enzymes, of which 24 isoforms are known in humans. These enzymes degrade the proteins of the extracellular matrix and play a role of utmost importance in the physiological remodeling of all tissues. However, certain MMPs, s...

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Autores principales: Laghezza, Antonio, Piemontese, Luca, Brunetti, Leonardo, Caradonna, Alessia, Agamennone, Mariangela, Loiodice, Fulvio, Tortorella, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912614/
https://www.ncbi.nlm.nih.gov/pubmed/33498946
http://dx.doi.org/10.3390/ph14020085
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author Laghezza, Antonio
Piemontese, Luca
Brunetti, Leonardo
Caradonna, Alessia
Agamennone, Mariangela
Loiodice, Fulvio
Tortorella, Paolo
author_facet Laghezza, Antonio
Piemontese, Luca
Brunetti, Leonardo
Caradonna, Alessia
Agamennone, Mariangela
Loiodice, Fulvio
Tortorella, Paolo
author_sort Laghezza, Antonio
collection PubMed
description Matrix Metalloproteinases (MMPs) are a family of secreted and membrane-bound enzymes, of which 24 isoforms are known in humans. These enzymes degrade the proteins of the extracellular matrix and play a role of utmost importance in the physiological remodeling of all tissues. However, certain MMPs, such as MMP-2, -9, and -13, can be overexpressed in pathological states, including cancer and metastasis. Consequently, the development of MMP inhibitors (MMPIs) has been explored for a long time as a strategy to prevent and hinder metastatic growth, but the important side effects linked to promiscuous inhibition of MMPs prevented the clinical use of MMPIs. Therefore, several strategies were proposed to improve the therapeutic profile of this pharmaceutical class, including improved selectivity toward specific MMP isoforms and targeting of specific organs and tissues. Combining both approaches, we conducted the synthesis and preliminary biological evaluation of a series of (2-aminobenzothiazole)-methyl-1,1-bisphosphonic acids active as selective inhibitors of MMP-13 via in vitro and in silico studies, which could prove useful for the treatment of bone metastases thanks to the bone-targeting capabilities granted by the bisphosphonic acid group.
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spelling pubmed-79126142021-02-28 (2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone Laghezza, Antonio Piemontese, Luca Brunetti, Leonardo Caradonna, Alessia Agamennone, Mariangela Loiodice, Fulvio Tortorella, Paolo Pharmaceuticals (Basel) Communication Matrix Metalloproteinases (MMPs) are a family of secreted and membrane-bound enzymes, of which 24 isoforms are known in humans. These enzymes degrade the proteins of the extracellular matrix and play a role of utmost importance in the physiological remodeling of all tissues. However, certain MMPs, such as MMP-2, -9, and -13, can be overexpressed in pathological states, including cancer and metastasis. Consequently, the development of MMP inhibitors (MMPIs) has been explored for a long time as a strategy to prevent and hinder metastatic growth, but the important side effects linked to promiscuous inhibition of MMPs prevented the clinical use of MMPIs. Therefore, several strategies were proposed to improve the therapeutic profile of this pharmaceutical class, including improved selectivity toward specific MMP isoforms and targeting of specific organs and tissues. Combining both approaches, we conducted the synthesis and preliminary biological evaluation of a series of (2-aminobenzothiazole)-methyl-1,1-bisphosphonic acids active as selective inhibitors of MMP-13 via in vitro and in silico studies, which could prove useful for the treatment of bone metastases thanks to the bone-targeting capabilities granted by the bisphosphonic acid group. MDPI 2021-01-24 /pmc/articles/PMC7912614/ /pubmed/33498946 http://dx.doi.org/10.3390/ph14020085 Text en © 2021 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 Communication
Laghezza, Antonio
Piemontese, Luca
Brunetti, Leonardo
Caradonna, Alessia
Agamennone, Mariangela
Loiodice, Fulvio
Tortorella, Paolo
(2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone
title (2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone
title_full (2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone
title_fullStr (2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone
title_full_unstemmed (2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone
title_short (2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone
title_sort (2-aminobenzothiazole)-methyl-1,1-bisphosphonic acids: targeting matrix metalloproteinase 13 inhibition to the bone
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912614/
https://www.ncbi.nlm.nih.gov/pubmed/33498946
http://dx.doi.org/10.3390/ph14020085
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