Dual-acting antitumor Pt(iv) prodrugs of kiteplatin with dichloroacetate axial ligands
| Autor: | Valentina Gandin, Cristina Marzano, Giovanni Natile, James D. Hoeschele, Nicola Margiotta, Salvatore Savino |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Organoplatinum Compounds Antineoplastic Agents Cell Death Cell Line Tumor Cell Proliferation Dichloroacetic Acid Drug Screening Assays Antitumor Humans Ligands Molecular Structure Prodrugs Reactive Oxygen Species Inorganic Chemistry Dichloroacetic acid Oxidative phosphorylation Pharmacology Mitochondrion Drug Screening Assays 010402 general chemistry 01 natural sciences Cell Line 03 medical and health sciences chemistry.chemical_compound medicine Inner mitochondrial membrane Cisplatin Tumor Chemistry Cell growth Antitumor Prodrug Ascorbic acid 0104 chemical sciences 030104 developmental biology medicine.drug |
| Zdroj: | Dalton transactions (Cambridge, England : 2003). 47(21) |
| ISSN: | 1477-9234 |
| Popis: | With the aim to obtain dual acting drugs able to target both nuclear DNA and mitochondria, Pt(iv) kiteplatin derivatives having dichloroacetate (DCA) ligands in axial positions have been synthesized. The rather fast hydrolysis (t1/2 of ca. 1 h) and reduction (by ascorbic acid) of these Pt(iv) derivatives did not impede a potent pharmacological effect on tumor cells. Moreover, similarly to kiteplatin, also the Pt(iv)-DCA compounds proved to be capable of overcoming oxaliplatin-resistance, which is particularly important in view of the fact that metastatic colorectal cancer is the third most common cancer in males and the second in females. The possible role of DCA released by the Pt(iv) compounds in eliciting the antiproliferative activity has also been investigated. Pt(iv)-DCA compounds determine a substantial increase of ROS production, blockage of oxidative phosphorylation, hypopolarization of the mitochondrial membrane, and caspase-3/7 mediated apoptotic cell death. |
| Databáze: | OpenAIRE |
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