Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes |
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Authors: | Emma S Child Savvas N Georgiades Kirsten N Rose Verity S Stafford Chirag B K Patel Joachim H G Steinke David J Mann Ramon Vilar |
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Institution: | (1) Division of Cell and Molecular Biology, Imperial College London, South Kensington, London, SW7 2AZ, UK;(2) Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK; |
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Abstract: | 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 metal-based 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. |
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Keywords: | Platinum Kinase Cdk Bioinorganic MAPK ERK Inhibitor |
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