Palladium(II)-η3-Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids
| Autor: | Scattolin, T., Bortolamiol, E., Visentin, F., Palazzolo, S., Caligiuri, I., Perin, T., Canzonieri, V., Demitri, N., Rizzolio, F., Togni, A. |
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| Přispěvatelé: | Scattolin, T., Bortolamiol, E., Visentin, F., Palazzolo, S., Caligiuri, I., Perin, T., Canzonieri, V., Demitri, N., Rizzolio, F., Togni, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
organoid
palladium allyl complexe Ligand Antineoplastic Agents Ligands Cell Line palladium allyl complexes Antineoplastic Agent Coordination Complexes Cell Line Tumor Humans allylation organoids Cell Proliferation Settore CHIM/03 - Chimica Generale e Inorganica Ovarian Neoplasms N-trifluoromethyl N-heterocyclic carbenes Tumor N-trifluoromethyl N-heterocyclic carbene Coordination Complexe Ovarian Neoplasm ovarian cancer Cisplatin Female Palladium Human |
| Popis: | The first palladium organometallic compounds bearing N-trifluoromethyl N-heterocyclic carbenes have been synthesized. These η3-allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC50 values fall in the range 0.02–0.5 μm). By choosing 1,3,5-triaza-7-phosphaadamantane (PTA) as co-ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2-methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η3-allyl fragment. The effectiveness of a representative complex, 4 c, was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids. |
| Databáze: | OpenAIRE |
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