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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| Veröffentlicht in: | Angewandte Chemie International Edition 2015-11, Vol.54 (48), p.14478-14482 |
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| container_title | Angewandte Chemie International Edition |
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| creator | Kasparkova, Jana Kostrhunova, Hana Novakova, Olga Křikavová, Radka Vančo, Ján Trávníček, Zdeněk Brabec, Viktor |
| description | 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. |
| doi_str_mv | 10.1002/anie.201506533 |
| format | Article |
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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.</description><subject>Anticancer properties</subject><subject>Antitumor agents</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>Genes</subject><subject>Genome</subject><subject>Histone deacetylase</subject><subject>histone deacetylase inhibitors</subject><subject>Histone Deacetylases - metabolism</subject><subject>Histones</subject><subject>Hydroxamic acid</subject><subject>Photoactivation</subject><subject>Photochemistry</subject><subject>Platinum</subject><subject>Platinum - chemistry</subject><subject>platinum prodrugs</subject><subject>Selectivity</subject><subject>Toxicity</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEURi0EoiWwZYkssSmLCbavX11GacmDKnRRytLyODdlysw4Hc9A8-9xSYkQC1j5yjrfZ-seQl5zNuaMife-rXAsGFdMK4An5JgrwQswBp7mWQIUxip-RF6kdJt5a5l-To6ElipP9phcT-jl19hHH_rqu-99WSO9rH1ftUNzsrh-R6ex2dZ4T698d4P5-obOsI1NFejZakJ9u6bzKvWxRXqGPmC_q33C9JI82_g64avHc0Q-fzi_ms6Li0-zxXRyUQQlBRQSpVYlM8FKBA1GeKk4GMUCNzYYa0tTKmmD9-GUCxZKQAZSb9S6NBzkGkbkZN-77eLdgKl3TZUC1rVvMQ7JcWO0VtYKyOjbv9DbOHRt_p0TSov8LDD7L4rnKmF-7XlExnsqdDGlDjdu21WN73aOM_fgxT14cQcvOfDmsXYoG1wf8N8iMnC6B35UNe7-U-cmq8X5n-XFPptF4P0h67tvTpu8TfdlNXPLuVlOOV-6j_ATdjqlJA</recordid><startdate>20151123</startdate><enddate>20151123</enddate><creator>Kasparkova, Jana</creator><creator>Kostrhunova, Hana</creator><creator>Novakova, Olga</creator><creator>Křikavová, Radka</creator><creator>Vančo, Ján</creator><creator>Trávníček, Zdeněk</creator><creator>Brabec, Viktor</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>K9.</scope></search><sort><creationdate>20151123</creationdate><title>A Photoactivatable Platinum(IV) Complex Targeting Genomic DNA and Histone Deacetylases</title><author>Kasparkova, Jana ; 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| 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 |
| title | A Photoactivatable Platinum(IV) Complex Targeting Genomic DNA and Histone Deacetylases |
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