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Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 16; Pages: 9397
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 23; Issue 16; Pages: 9397
- Accession number :
- edsair.doi.dedup.....09090187850091ebeaeb02bc55b074f9
- Full Text :
- https://doi.org/10.3390/ijms23169397