Transcription Inhibition by Organometallic Ruthenium-Arene Anticancer Complexes in Live Mammalian Cells.

Organometallic ruthenium-arene RAPTA complexes, currently being actively pursued as potential anticancer agents, interact with intracellular biological targets to form covalent adducts. Because their mode of action is still unclear, we investigated their binding with DNA and the ability of ruthenated-DNA adducts to elicit cellular responses such as transcription inhibition and repair. To investigate the influence of the spectator arene ligands on RAPTA activity, a novel RAPTA complex containing the bulky 1,3,5-triisopropylbenzene ligand was synthesized and characterized. Transcription experiments carried out in live mammalian cells using ruthenated plasmid probes revealed that increasing steric bulk of the arene ligand did not improve its ability to arrest transcription. Transcription experiments carried out in live mammalian cells using plasmid probes damaged by RAPTA complexes revealed that increasing steric bulk of arene ligand does not improve their ability to arrest transcription. [ABSTRACT FROM AUTHOR]