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
Google Scholar check
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2 and Cdk2 Felekkis, Kyriacos N.; Koupepidou, P.; Kastanos, E.; Witzgall, R.; Bai, C. -X; Li, L.; Tsiokas, L.; Gretz, N.; Constantinou-Deltas, Constantinos D. (2008)Background. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genes ...
Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27Kip1-dependent G1/S cell cycle arrest in conjunction with NF-κB activation Batsi, Christina; Markopoulou, Soultana; Kontargiris, Evangelos; Charalambous, Christina; Thomas, Christoforos G.; Christoforidis, Savvas; Kanavaros, Panagiotis E.; Constantinou, Andreas I.; Marcu, Kenneth B.; Kolettas, Evangelos (2009)2-Methoxyestradiol (2-ME2) induces leukemia cells to undergo apoptosis in association with Bcl-2 inactivation but the mechanisms whereby Bcl-2 contributes to protection against programmed cell death in this context remain ...
Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma Apidianakis, Yiorgos; Mindrinos, M. N.; Xiao, W.; Tegos, G. P.; Papisov, M. I.; Hamblin, M. R.; Davis, R. W.; Tompkins, R. G.; Rahme, L. G. (2007)Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and ...