Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes
AuthorChild, E. S.
Georgiades, Savvas N.
Rose, K. N.
Stafford, V. S.
Patel, C. B. K.
Steinke, J. H. G.
Mann, D. J.
SourceJournal of Chemical Biology
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Inhibition of protein kinases in the fight against disease remains a constant challenge for medicinal chemists, who have screened multitudes of predominantly planar organic scaffolds, natural and synthetic, to identify potent - albeit not always selective - kinase inhibitors. Herein, in an effort to investigate the potential biological utility of metalbased compounds as inhibitors against the cancer-relevant targets mitogen-activated protein kinase and cyclin-dependent kinase 2, we explore various parameters in planar platinum(II) complexes with substituted phenanthroline ligands and aliphatic diamine chelate co-ligands, to identify combinations that yield promising inhibitory activity. The individual ligands' steric requirements as well as their pattern of hydrogen bond donors/acceptors appear to alter inhibitory potency when modulated. © Springer-Verlag 2011.
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