Cytotoxicity-boosting of kiteplatin by Pt(IV) prodrugs with axial benzoate ligands
| Autor: | Nicola Margiotta, Cristina Marzano, Valentina Gandin, Salvatore Savino, James D. Hoeschele, Giovanni Natile, Concetta Pacifico |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Drug Cell growth inhibition Organoplatinum Compounds Cell Survival media_common.quotation_subject Antineoplastic Agents Crystallography X-Ray Ligands 010402 general chemistry Benzoates 01 natural sciences Biochemistry Inorganic Chemistry Cell Line Tumor medicine Humans Cytotoxic T cell Prodrugs Cytotoxicity Platinum media_common Cisplatin Kiteplatin Benzoate ligands 010405 organic chemistry Chemistry Pt(IV) complexes Biological Transport Biological activity Prodrug X-ray crystal structure 0104 chemical sciences Oxaliplatin A549 Cells Drug Resistance Neoplasm Lipophilicity Cancer cell MCF-7 Cells Cellular accumulation medicine.drug |
| Popis: | Kiteplatin, the neglected drug analogous of cisplatin but containing cis-1,4-DACH in place of the two ammines, has been recently reevaluated for its activity against cisplatin- and oxaliplatin-resistant tumors, in particular colo-rectal cancer. With the aim of further improving the pharmacological activity of this drug, Pt(IV) prodrugs were derived by addition of two, differently substituted, benzoate groups in axial positions (X-ray structure). The cytotoxic activity of both compounds resulted markedly potentiated reaching nanomolar concentration against a wide panel of human cancer cells. The ability of benzoate ligands to enhance the activity of kiteplatin most likely originates from their lipophilicity promoting a higher drug accumulation in cancer cells; however, it is to be noted that the increase in pharmacological effect is far greater than the increase in cellular uptake. Overcoming cisplatin- and oxaliplatin-resistance by kiteplatin derivatives appears to relate to the inability of membrane extrusion pumps to remove active Pt species from tumor cells. |
| Databáze: | OpenAIRE |
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