Complementing organic elements with a metal center provides new opportunities for
building three-dimensional structures with unique and defined shapes. Such access
to unexplored chemical space may lead to the discovery of molecules with unprecedented
properties. Along these lines, this account article describes our successful design
of highly potent and selective ruthenium-based inhibitors for the protein kinases
GSK-3 and Pim-1 by using the class of indolocarbazole alkaloids as a lead structure.
The described ruthenium complexes are kinetically inert scaffolds in which the ruthenium
has the function to organize the orientation of the organic ligands in the three-dimensional
space.
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1 Introduction
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1.1 Biologically Relevant Chemical Space
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1.2 Organic vs. Organometallic Compounds
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1.3 Ruthenium as a Virtual Octahedral Carbon
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2 Mimicking the Natural Product Staurosporine with Simple Ruthenium Complexes
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3 Synthesis of Cycloruthenated Pyrido[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-diones
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4 Discovery of Ruthenium Complexes as Protein Kinase Inhibitors
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4.1 Octahedral Complexes
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4.2 Half-Sandwich Complexes
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5 Structures of Ruthenium Half-Sandwich Complexes Bound to Protein Kinase Pim-1
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6 GSK-3 Inhibition in Mammalian Cells, Frog Embryos, and Zebrafish Embryos
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7 Summary and Outlook
bioorganometallic chemistry - protein kinases - inhibitors - ruthenium - mammalian
cells
