| Autor: |
Nordio G; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.; Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), 50121 Firenze, Italy., Piazzola F; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy., Cozza G; Department of Molecular Medicine, University of Padova, 35131 Padova, Italy., Rossetto M; Department of Molecular Medicine, University of Padova, 35131 Padova, Italy., Cervelli M; Department of Science, University of Rome 'Roma Tre', 00146 Rome, Italy., Minarini A; Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy., Basagni F; Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy., Tassinari E; Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921 Rimini, Italy., Dalla Via L; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.; Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), 50121 Firenze, Italy., Milelli A; Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921 Rimini, Italy., Di Paolo ML; Department of Molecular Medicine, University of Padova, 35131 Padova, Italy. |
| Abstrakt: |
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. |
