Molecules (Aug 2023)

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

DOI
https://doi.org/10.3390/molecules28176329
Journal volume & issue
Vol. 28, no. 17
p. 6329

Abstract

Read online

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 50 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity.

Keywords