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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7912614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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