A novel class of light activated cytotoxic agents, centering on a ruthenium scaffold, have been synthesized and found to covalently interact with DNA.  Several of the compounds have low toxicity in the absence of light, where viability in several cell lines is not reduced until concentrations of 300 micromolar, but upon light activation, cellular cytotoxicities occur at low micromolar concentrations.  In vitro analysis demonstrated crosslinking to plasmid DNA upon light activation, while in vivo the compounds appear to induce apoptosis as determined by western blot analysis.  Cell cycle analysis indicates that the known DNA crosslinking drug, cisplatin, induces an S-phase arrest in HL60 cells while in contrast the ruthenium compounds populate a sub-G1 phase.  The mechanism is further explored to identify other possible routes responsible for this light driven toxicity.

Mechanism of action of novel light activated cytotoxic ruthenium compounds

243rd National Meeting (2012)

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