Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands
| Autor: | Maura Pellei, Carlo Santini, Luca Bagnarelli, Chiara Battocchio, Giovanna Iucci, Iole Venditti, Carlo Meneghini, Simone Amatori, Paolo Sgarbossa, Cristina Marzano, Michele De Franco, Valentina Gandin |
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| Přispěvatelé: | Pellei, Maura, Santini, Carlo, Bagnarelli, Luca, Battocchio, Chiara, Iucci, Giovanna, Venditti, Iole, Meneghini, Carlo, Amatori, Simone, Sgarbossa, Paolo, Marzano, Cristina, De Franco, Michele, Gandin, Valentina |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
XAS
Ligand Acetates Ligands Crystallography X-Ray Catalysis Inorganic Chemistry Coordination Complexes Humans Ester Physical and Theoretical Chemistry Molecular Biology bis(pyrazolyl)acetate ligands Spectroscopy bis(pyrazolyl)acetate ligand Crystallography Coordination Complexe SR-XPS Acetate Organic Chemistry Esters General Medicine Computer Science Applications copper cytotoxicity Cisplatin Copper X-Ray Human |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 16; Pages: 9397 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23169397 |
| Popis: | Bis(pyrazol-1-yl)acetic acid (HC(pz)2COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pzMe2)2COOH) were converted into the methyl ester derivatives 1 (LOMe) and 2 (L2OMe), respectively, and were used for the preparation of Cu(I) and Cu(II) complexes 3–10. The copper(II) complexes were prepared by the reaction of CuCl2·2H2O or CuBr2 with ligands 1 and 2 in methanol solution. The copper(I) complexes were prepared by the reaction of Cu[(CH3CN)4]PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine with LOMe and L2OMe in acetonitrile solution. Synchrotron radiation-based complementary techniques (XPS, NEXAFS, and XAS) were used to investigate the electronic and molecular structures of the complexes and the local structure around copper ions in selected Cu(I) and Cu(II) coordination compounds. All Cu(I) and Cu(II) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human cancer cell lines, and were able to overcome cisplatin resistance. Noticeably, Cu complexes appeared much more effective than cisplatin in 3D spheroid cultures. Mechanistic studies revealed that the antitumor potential did not correlate with cellular accumulation but was consistent with intracellular targeting of PDI, ER stress, and paraptotic cell death induction. |
| Databáze: | OpenAIRE |
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