From Monoamine Oxidases Inhibition to Antiproliferative Activity: New Biological Perspective for Polyamine Analogs

Giulia Nordio; Francesco Piazzola; Giorgio Cozza; Monica Rossetto; Manuela Cervelli; Anna Minarini; Filippo Basagni; Elisa Tassinari; Lisa Dalla Via; Andrea Milelli; Maria Luisa Di Paolo

doi:10.20944/preprints202308.0458.v1

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202308.0458.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

From Monoamine Oxidases Inhibition to Antiproliferative Activity: New Biological Perspective for Polyamine Analogs

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Version 1 : Received: 3 August 2023 / Approved: 4 August 2023 / Online: 7 August 2023 (11:57:36 CEST)

A peer-reviewed article of this Preprint also exists.

Nordio, G.; Piazzola, F.; Cozza, G.; Rossetto, M.; Cervelli, M.; Minarini, A.; Basagni, F.; Tassinari, E.; Via, L.D.; Milelli, A.; Di Paolo, M.L. From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs. Molecules 2023, 28, 6329. Nordio, G.; Piazzola, F.; Cozza, G.; Rossetto, M.; Cervelli, M.; Minarini, A.; Basagni, F.; Tassinari, E.; Via, L.D.; Milelli, A.; Di Paolo, M.L. From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs. Molecules 2023, 28, 6329.

Abstract

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, where they have been found overexpressed. This finding is opening new frontiers for MAOs inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAOs inhibitor, our aim was to search for novel analogues with even greater inhibitory potency for human MAOs and, possibly, endowed with antiproliferative activity. A small in house library of polyamine analogs (2-7) was selected to investigate the effect of a constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compound 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety emerged as the most potent, reversible and mainly competitive MAO inhibitors (Ki < 1uM). Additionally, they exhibited a high antiproliferative activity in three tumor cell lines, in particular in the LN-229 line, a glioblastoma model (GI50 < 1uM). The scaffold of compound 5, in particular, could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity.

Keywords

polyamine analogs; monoamine oxidases; antiproliferative activity; inhibitors; docking studies; LN-229 cells

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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