Abstract
AbstractDinuclear trihydroxido‐bridged osmium–arene complexes are inert and biologically inactive, but we show here that linking dihydroxido‐bridged OsII–arene fragments by a bridging di‐imine to form a metallacycle framework results in strong antiproliferative activity towards cancer cells and distinctive knotting of DNA. The shortened spacer length reduces biological activity and stability in solution towards decomposition to biologically inactive dimers. Significant differences in behavior toward plasmid DNA condensation are correlated with biological activity.
Highlights
Platinum drugs are used in over 50 % of all chemotherapeutic regimens.[1]
Resistance to Pt drugs is a clinical drawback that might be overcome by designing new drugs that induce distinctly different conformational changes in DNA.[3]
We show that the length of the linker is critical for maintaining stability of the tetranuclear assembly in solution, inducing DNA binding and enhancing antiproliferative activity towards human cancer cells
Summary
Platinum drugs are used in over 50 % of all chemotherapeutic regimens.[1]. The basis for their activity is believed to be mainly due to DNA binding, in particular to changes in DNA conformation.[2]. We link inert biologically inactive dinuclear hydroxido-bridged OsII arene units to form active tetranuclear complexes that can induce DNA knotting.
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