TY - JOUR
T1 - Computational and experimental evaluation of ornithine derivatives as ornithine decarboxylase inhibitors
AU - Correa-Basurto, J.
AU - Rodríguez-Páez, L.
AU - Aguiar-Moreno, E. S.
AU - López-Sánchez, P.
AU - Espinoza-Fonseca, L. M.
AU - Wong, C.
AU - Trujillo-Ferrara, J.
N1 - Funding Information:
Acknowledgment This work was partially supported by grant 46217 and 62488 from CONACyT and grants 20070566, 20070140, 20060047, and 20060196 from COFAA-SIP/IPN.
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
KW - Docking
KW - Ornithine analogues
KW - Ornithine decarboxylase
KW - Polyamines
UR - http://www.scopus.com/inward/record.url?scp=58249103392&partnerID=8YFLogxK
U2 - 10.1007/s00044-008-9103-6
DO - 10.1007/s00044-008-9103-6
M3 - Artículo
SN - 1054-2523
VL - 18
SP - 20
EP - 30
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 1
ER -