Palladium (II) complexes as inhibitors of cathepsin B and topoisomerase I beta: Synthesis, characterization, and cytotoxicity

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Akinyemi, Amos O. ; Pereira, George B. S. ; Oliveira, Gabriela P. ; Lima, Mauro A. ; Rocha, Josias S. ; Costa, Vinicius A. ; Fortaleza, Dario B. ; Teixeira, Tamara ; Zanotti, Karine ; Forim, Moacir Rossi ; Araujo-Neto, Joao H. ; Ellena, Javier ; Rocha, Fillipe Vieira

• Document type: Journal article
• Source: Journal of Molecular Structure; v. 1294, p. 14-pg., 2023-12-15.

Abstract

This research presents the synthesis, characterization, anticancer activity, and investigation of biological targets of three new palladium (II) complexes. The compounds were characterized by spectroscopies techniques (UV-Vis, NMR, and IR), elemental analysis, mass spectrometry, and one for monocrystal X-ray diffraction. The cytotoxic activity of the complexes against two cell lines, A2780cis (cisplatin resistance ovarian tumor cell line) and MRC-5 (non-tumor lung cell), was evaluated. The in vitro cytotoxicity assays using the MTT method revealed a significant cytotoxic activity of the palladium complexes against the evaluated cell lines, highlighting the resistance tumor cell line, A2780cis. Also, DNA interaction studies suggested that the compounds either do not interact, or interact weakly with DNA via groove and/or electrostatically. The interaction assay demonstrated that the compounds can weakly to moderately bind to the HSA biomolecule through electrostatic or van der Waals forces. In addition, agarose gel electrophoresis assays indicated that the complexes could not inhibit the action of the enzyme, topoisomerase II alpha. Nonetheless, the complexes demonstrated a promising target against topoisomerase I beta by promoting its inhibition. Finally, fluorescence studies revealed the capacity of irreversible inhibition of the complexes against the enzyme, cathepsin B. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) antioxidant assay did not show significant scavenging of DPPH radical. The results showed that the proposed structural features generate compounds of high cytotoxicity that can inhibit the action of cathepsin B and topoisomerase I beta. (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: 21/04876-4 - Studies on structure & activity of RuII / arene / mercaptoligants complexes against cancer
• Grantee: João Honorato de Araujo Neto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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