Cytotoxicity assay and gene expression studies of acylpyrazolone-based square planar Cu(II) complexes: synthesis, characterization and computations

Abstract

We employed a dual strategy that combines experimental and computational analyses of two copper(II) coordination complexes with σ-donating acylpyrazolone ligands. HL^IIIB, [Cu(HL^IIIB)₂] and [Cu(HL^I)₂] have been characterized using a variety of physicochemical methods and density functional theory (DFT) calculations using the B3LYP level of theory and 6-31 G basis set. Single crystal X-ray diffraction studies revealed monoclinic and triclinic crystal systems for [Cu(HL^I)₂] and [Cu(HL^IIIB)₂], respectively, with square planar geometries for both complexes. Both complexes exhibit quasi-reversible behavior in their cyclic voltammograms in DMSO. ESR spectroscopy was performed to determine the magnetic behaviorof the two complexes. The intermolecular interactions of the complexes were further investigated using Hirshfeld surface analysis. The compounds showed promising cytotoxicities when tested against cancer cell lines of lung carcinoma, hepatocellular carcinoma, and neuroblastoma. Notable apoptotic cell death was observed with [Cu(HL^I)₂], supported by gene expression changes, indicating induction of apoptosis. The findings suggest the potential of copper complexes as effective agents against neuroblastoma and highlight their superiority to cisplatin.

KEYWORDS:

• Acylpyrazolone ligand
• Hirshfeld analysis
• DFT (density functional theory)
• gene expression
• MTT assay

Accession codes

Crystallographic information for the structural study has been submitted to the Cambridge Crystallographic Data Center under CCDC Nos. 2263829-2263831. The Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ (UK), can be reached by Fax at [phone] or E-mail at [email protected] for free access to these data.

Acknowledgements

The authors are thankful to the Head, Department of Chemistry, The Maharaja Sayajirao University of Baroda, for providing the facilities and offering the requisite centres to carry out this work. Thanks to Mr. Jeet Sharma, CSIR-CSMCRI, Bhavnagar for the Electro-chemical analysis (CV).

Disclosure statement

The authors emphasize that they are not aware of any personal or financial conflicts that might have appeared to affect the research described in this paper.

Additional information

Funding

Government, non-profit, or corporate organizations did not sponsor this research in any way.