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From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs

Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is...

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Autores principales: Nordio, Giulia, Piazzola, Francesco, Cozza, Giorgio, Rossetto, Monica, Cervelli, Manuela, Minarini, Anna, Basagni, Filippo, Tassinari, Elisa, Dalla Via, Lisa, Milelli, Andrea, Di Paolo, Maria Luisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10490032/
https://www.ncbi.nlm.nih.gov/pubmed/37687158
http://dx.doi.org/10.3390/molecules28176329
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author Nordio, Giulia
Piazzola, Francesco
Cozza, Giorgio
Rossetto, Monica
Cervelli, Manuela
Minarini, Anna
Basagni, Filippo
Tassinari, Elisa
Dalla Via, Lisa
Milelli, Andrea
Di Paolo, Maria Luisa
author_facet Nordio, Giulia
Piazzola, Francesco
Cozza, Giorgio
Rossetto, Monica
Cervelli, Manuela
Minarini, Anna
Basagni, Filippo
Tassinari, Elisa
Dalla Via, Lisa
Milelli, Andrea
Di Paolo, Maria Luisa
author_sort Nordio, Giulia
collection PubMed
description Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is opening new frontiers for MAO inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAO inhibitor, our aim was to search for novel analogs with greater inhibitory potency for human MAOs and possibly with antiproliferative activity. A small in-house library of polyamine analogs (2–7) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety, emerged as the most potent, reversible, and mainly competitive MAO inhibitors (Ki < 1 μM). Additionally, they exhibited a high antiproliferative activity in the LN-229 human glioblastoma cell line (GI(50) < 1 μM). The scaffold of compound 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity.
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spelling pubmed-104900322023-09-09 From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs Nordio, Giulia Piazzola, Francesco Cozza, Giorgio Rossetto, Monica Cervelli, Manuela Minarini, Anna Basagni, Filippo Tassinari, Elisa Dalla Via, Lisa Milelli, Andrea Di Paolo, Maria Luisa Molecules Article Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is opening new frontiers for MAO inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAO inhibitor, our aim was to search for novel analogs with greater inhibitory potency for human MAOs and possibly with antiproliferative activity. A small in-house library of polyamine analogs (2–7) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety, emerged as the most potent, reversible, and mainly competitive MAO inhibitors (Ki < 1 μM). Additionally, they exhibited a high antiproliferative activity in the LN-229 human glioblastoma cell line (GI(50) < 1 μM). The scaffold of compound 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity. MDPI 2023-08-29 /pmc/articles/PMC10490032/ /pubmed/37687158 http://dx.doi.org/10.3390/molecules28176329 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nordio, Giulia
Piazzola, Francesco
Cozza, Giorgio
Rossetto, Monica
Cervelli, Manuela
Minarini, Anna
Basagni, Filippo
Tassinari, Elisa
Dalla Via, Lisa
Milelli, Andrea
Di Paolo, Maria Luisa
From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs
title From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs
title_full From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs
title_fullStr From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs
title_full_unstemmed From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs
title_short From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs
title_sort from monoamine oxidase inhibition to antiproliferative activity: new biological perspectives for polyamine analogs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10490032/
https://www.ncbi.nlm.nih.gov/pubmed/37687158
http://dx.doi.org/10.3390/molecules28176329
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