Synthesis and Biological Evaluation of Guanidino Compounds Endowed with Subnanomolar Affinity as Competitive Inhibitors of Maize Polyamine Oxidase

Previous studies on agmatine and its derivatives suggested that the presence of hydrophobic groups on the guanidine moiety was a crucial key for inhibitory activity of maize polyamine oxidase. Accordingly, new lipophilic agmatine and iminoctadine derivatives were synthesized and tested for their abi...

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Veröffentlicht in:	Journal of medicinal chemistry 2009-08, Vol.52 (15), p.4774-4785
Hauptverfasser:	Manetti, Fabrizio, Cona, Alessandra, Angeli, Lucilla, Mugnaini, Claudia, Raffi, Francesco, Capone, Caterina, Dreassi, Elena, Zizzari, Alessandra Tania, Tisi, Alessandra, Federico, Rodolfo, Botta, Maurizio
Format:	Artikel
Sprache:	eng
Schlagworte:	Agmatine - analogs & derivatives Agmatine - pharmacology Binding Sites Binding, Competitive Biological and medical sciences Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacokinetics Enzyme Inhibitors - pharmacology Guanidines - chemical synthesis Guanidines - pharmacokinetics Guanidines - pharmacology Medical sciences Miscellaneous Oxidoreductases Acting on CH-NH Group Donors - antagonists & inhibitors Pharmacology. Drug treatments Polyamine Oxidase Structure-Activity Relationship Zea mays - enzymology
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Zusammenfassung:	Previous studies on agmatine and its derivatives suggested that the presence of hydrophobic groups on the guanidine moiety was a crucial key for inhibitory activity of maize polyamine oxidase. Accordingly, new lipophilic agmatine and iminoctadine derivatives were synthesized and tested for their ability to inhibit this enzyme. Several compounds showed an affinity in the nanomolar range, while a cyclopropylmethyl derivative of iminoctadine was found to be the most potent inhibitor of maize polyamine oxidase reported so far (K i = 0.08 nM).
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm900371z