Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 54, Issue 48, Pages 14478-14482Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201506533
Keywords
antitumor agents; DNA; histone deacetylase inhibitors; photoactivation; platinum prodrugs
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Funding
- Czech Science Foundation [14-21053S]
- Ministry of Education, Youth and Sports of the CR [LD14019]
- National Program of Sustainability I of the Ministry of Education, Youth and Sports of the Czech Republic [LO1305]
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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.
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