From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives 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
Author Information
Giulia Nordio: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
Francesco Piazzola: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
Giorgio Cozza: Department of Molecular Medicine, University of Padova, 35131 Padova, Italy. ORCID
Monica Rossetto: Department of Molecular Medicine, University of Padova, 35131 Padova, Italy. ORCID
Manuela Cervelli: Department of Science, University of Rome "Roma Tre", 00146 Rome, Italy. ORCID
Anna Minarini: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy. ORCID
Filippo Basagni: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy. ORCID
Elisa Tassinari: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921 Rimini, Italy.
Lisa Dalla Via: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy. ORCID
Andrea Milelli: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921 Rimini, Italy. ORCID
Maria Luisa Di Paolo: Department of Molecular Medicine, University of Padova, 35131 Padova, Italy. ORCID
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 (-) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds and , characterized by a dianiline () or dianilide () 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 < 1 μM). The scaffold of compound could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity.
