Molecular Biophysics and Pharmacology
A Photoactivatable Platinum( IV) Complex Targeting Genomic DNA and Histone Deacetylases
Published: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 54, 14478-14482 Authors: Kasparkova, J., Kostrhunova, H., Novakova, O., Krikavova, R., Vanco, J., Travnicek, Z., Brabec, V. Year: 2015
We report toxic effects of a photoactivatable platinum(IV) complex conjugated with suberoyl-bis-hydroxamic acid in tumor cells. The conjugate exerts, after photoactivation, two functions: activity as both a platinum(II) anticancer drug and histone deacetylase (HDAC) inhibitor in cancer cells. This approach relies on the use of a Pt-IV pro-drug, acting by two independent mechanisms of biological action in a cooperative manner, which can be selectively photoactivated to a cytotoxic species in and around a tumor, thereby increasing selectivity towards cancer cells. These results suggest that this strategy is a valuable route to design new platinum agents with higher efficacy for photodynamic anticancer chemotherapy.