New polyamine derivatives 1-8, related to the previously reported N(1),N(12)-dibenzyldodecane-1,12-diamine (Bis-Bza-Diado) and N(1)-benzyl-spermine (BD6), have been synthesized and used as "probes" (potential substrates or inhibitors) of the human monoamine oxidases (MAO A and MAO B) and Vascular-Adhesion-protein -1 (VAP-1). Compound 8, the most effective inhibitor of the series, is characterized by a 12-methylene carbon chain ending with an isothiocyanate (ITC) group. Interestingly, it behaves as competitive inhibitor of MAO B and as irreversible inhibitor of MAO A. Compound 3, an asymmetric spermine analogue bearing a thiophene ring, acts as a reversible mixed inhibitor, selective for MAO B (K(IE) = 23 μM). Docking studies performed using the available Protein Data Bank (PDB) structures of MAO A and MAO B, suggested that the different mode of inhibition of 8 may be explained by the different binding poses of 8 into the active site cavities of the two MAO isoforms. The ε-amino group of Lys 305 of MAO A is proposed as possible target of the ITC group of the inhibitor. Further studies are in progress to confirm this hypothesis. These results indicate a potential use of the polyamine scaffold for the development of new MAO inhibitors for application in human pathologies involving these enzymes.