Antitumor Activity of New Pd(II) Complexes with Ligands Derived from O-Vanillin Acting as Topoisomerase I and II Inhibitors

Author(s)

Franco, Mariane A. ; Guedes, Adriana P. M. ; Batista, Alzir A. ; Deflon, Victor M. ; Akinyemi, Amos O. ; Rocha, Josias S. ; Rocha, Fillipe V.

• Document type: Journal article
• Source: CHEMISTRYSELECT; v. 9, n. 31, p. 8-pg., 2024-08-20.

Abstract

This study investigates topoisomerase I and II enzyme inhibition by novel Pd(II) complexes. TSC represents the chelating ligand thiosemicarbazone, which is modified at its 4(N)-nitrogen terminal position with substituents such as C2H(5), CH3, and H. PR3 represents the triphenylphosphine ligand, with positional variations including para substituents H, F, OCH3, and CH3. The aim is to establish a correlation between these molecular variations and cytotoxicity. In particular, the compounds show promising cytotoxicity against MDA-MB-231 and A549 tumor cell lines, especially those with H substitution at the terminal position 4(N) of TSC and H and F in the triphenylphosphine. The results suggest that a smaller molecular volume of ligand substituents may enhance the cytotoxic effects. The inhibitory potential of the complexes against DNA topoisomerase enzymes was investigated. The IC50 values of the most promising complexes strongly inhibit TOPOII alpha and TOPOI beta, suggesting these enzymes as primary targets. These complexes exhibited significantly lower IC50 values (4.32-4.88 mu M) compared to cisplatin (10.2 mu M) against MDA-MB-231 cells, indicating a distinct mode of action. However, it is noteworthy that the complexes did not inhibit the action of DNA topoisomerase II beta, suggesting selectivity against specific isoforms of DNA topoisomerase II that act as catalytic inhibitors. (AU)

• FAPESP's process: 19/11242-1 - Relative quantification of DNA-Topoisomerases enzymes in cell lines: Correlation between cytotoxicity and mechanism of action of coordination compounds
• Grantee: Fillipe Vieira Rocha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/02876-0 - Evaluation of the biological profile of coordination complexes: an approach in 2D and 3D cell models
• Grantee: Fillipe Vieira Rocha
• Support Opportunities: Regular Research Grants