A Photoactivatable Platinum(IV) Complex Targeting Genomic DNA and Histone Deacetylases

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 a...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2015-11, Vol.54 (48), p.14478-14482
Main Authors: Kasparkova, Jana, Kostrhunova, Hana, Novakova, Olga, Křikavová, Radka, Vančo, Ján, Trávníček, Zdeněk, Brabec, Viktor
Format: Article
Language:English
Subjects:
Anticancer properties
Antitumor agents
Cancer
Chemotherapy
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA - chemistry
Genes
Genome
Histone deacetylase
histone deacetylase inhibitors
Histone Deacetylases - metabolism
Histones
Hydroxamic acid
Photoactivation
Photochemistry
Platinum
Platinum - chemistry
platinum prodrugs
Selectivity
Toxicity
Tumor cells
Tumors
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Summary: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 PtIV 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. Two‐in‐one platinum anticancer drugs: The strategies based on simultaneous inhibition of histone deacetylases and DNA damage by platinum drugs induced by light may result in efficient antitumor activity taking advantages of selective and targeted activation in tumor cells.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201506533