Computational and experimental evaluation of ornithine derivatives as ornithine decarboxylase inhibitors

Polyamines play a relevant role in living cells because they are involved in several biological processes such as cell proliferation, transcription, and translation. In this article, we report the synthesis and in vitro evaluation of an ornithine analogue (6) as an ornithine decarboxylase (ODC) inhibitor. Docking studies of ornithine and some of its derivatives (1-6) on ODC were performed. The results showed that the affinity of 6 for ODC was lower than iodide compounds (4 and 5) by both docking simulations and kinetic experiments. However, the former was less toxic than 4 and 5. Finally, it is important to mention that the docking procedure showed several interactions between the ligands on Cys 360 and pyridoxal 5′phosphate (PLP), which could explain in part their ODC inhibitory effects.