title: A Photoactivatable Platinum(IV) Complex Targeting Genomic DNA and Histone Deacetylases.
abstract: 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.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 61265 Brno (Czech Republic). jana@ibp.cz.
authors.forename: Jana
authors.initials: J
authors.lastname: Kasparkova
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 61265 Brno (Czech Republic).
authors.forename: Hana
authors.initials: H
authors.lastname: Kostrhunova
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 61265 Brno (Czech Republic).
authors.forename: Olga
authors.initials: O
authors.lastname: Novakova
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacky University in Olomouc, 17. listopadu 12, 77146 Olomouc (Czech Republic).
authors.forename: Radka
authors.initials: R
authors.lastname: Křikavová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacky University in Olomouc, 17. listopadu 12, 77146 Olomouc (Czech Republic).
authors.forename: Ján
authors.initials: J
authors.lastname: Vančo
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacky University in Olomouc, 17. listopadu 12, 77146 Olomouc (Czech Republic).
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 61265 Brno (Czech Republic).|Department of Biophysics, Faculty of Science, Palacky University in Olomouc, 17. listopadu 12, 77146 Olomouc (Czech Republic).
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
mesh_terms: D004247:DNA / Q000737:chemistry*; D016678:Genome; D006655:Histone Deacetylases / Q000378:metabolism*; D010777:Photochemistry; D010984:Platinum / Q000737:chemistry*
chemical_list: D010984:Platinum; D004247:DNA; D006655:Histone Deacetylases
keywords: DNA; antitumor agents; histone deacetylase inhibitors; photoactivation; platinum prodrugs