TY - JOUR
T1 - Similar biological activities of two isostructural ruthenium and osmium complexes
AU - Maksimoska, Jasna
AU - Williams, Douglas S.
AU - Atilla-Gokcumen, G. Ekin
AU - Smalley, Keiran S.M.
AU - Carroll, Patrick J.
AU - Webster, Richard D.
AU - Filippakopoulos, Panagis
AU - Knapp, Stefan
AU - Herlyn, Meenhard
AU - Meggers, Eric
PY - 2008/5/29
Y1 - 2008/5/29
N2 - In this study, we probe and verify the concept of designing unreactive bioactive metal complexes, in which the metal possesses a purely structural function, by investigating the consequences of replacing ruthenium in a bioactive half-sandwich kinase inhibitor scaffold by its heavier congener osmium. The two isostructural complexes are compared with respect to their anticancer properties in 1205 Lu melanoma cells, activation of the Wnt signaling pathway, IC50 values against the protein kinases GSK-3β and Pim-1, and binding modes to the protein kinase Pim-1 by protein crystallography. It was found that the two congeners display almost indistinguishable biological activities, which can be explained by their nearly identical three-dimensional structures and their identical mode of action as protein kinase inhibitors. This is a unique example in which the replacement of a metal in an anticancer scaffold by its heavier homologue does not alter its biological activity.
AB - In this study, we probe and verify the concept of designing unreactive bioactive metal complexes, in which the metal possesses a purely structural function, by investigating the consequences of replacing ruthenium in a bioactive half-sandwich kinase inhibitor scaffold by its heavier congener osmium. The two isostructural complexes are compared with respect to their anticancer properties in 1205 Lu melanoma cells, activation of the Wnt signaling pathway, IC50 values against the protein kinases GSK-3β and Pim-1, and binding modes to the protein kinase Pim-1 by protein crystallography. It was found that the two congeners display almost indistinguishable biological activities, which can be explained by their nearly identical three-dimensional structures and their identical mode of action as protein kinase inhibitors. This is a unique example in which the replacement of a metal in an anticancer scaffold by its heavier homologue does not alter its biological activity.
KW - Antitumor agents
KW - Bioorganometallic chemistry
KW - Kinase inhibitors
KW - Osmium
KW - Ruthenium
UR - http://www.scopus.com/inward/record.url?scp=53849130664&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53849130664&partnerID=8YFLogxK
U2 - 10.1002/chem.200800294
DO - 10.1002/chem.200800294
M3 - Article
C2 - 18425743
AN - SCOPUS:53849130664
SN - 0947-6539
VL - 14
SP - 4816
EP - 4822
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 16
ER -