Synthesis, characterization, cytotoxicity study, interaction with DNA and topoisomerase IIα of square-planar complexes with thiosemicarbazones

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Silva, Ludimila Thayane Paes ; Pereira, George Bueno Santana ; de Oliveira, Gabriela Porto ; Lima, Mauro Almeida ; de Araujo Neto, Joao Honorato ; Akinyemi, Amos Olalekan ; Vieira, Marcelle Alcantara ; Nascimento-Junior, Nailton Monteiro ; de Farias, Renan Lira ; Ellena, Javier Alcides ; de Godoy Netto, Adelino Vieira ; Rocha, Fillipe Vieira

• Document type: Journal article
• Source: Polyhedron; v. 257, p. 9-pg., 2024-05-07.

Abstract

In this study, we report the synthesis and characterization of eight new palladium complexes and a nickel complex containing thiosemicarbazone ligands derived from chalcones and benzalketones. The techniques of Infrared and UV-visible spectroscopy, Nuclear Magnetic Resonance, Mass Spectrometry, and Elemental Analysis fully characterized the compounds. Crystallography was successful for five complexes and two ligands, allowing for X-ray Diffraction analysis. Molecular docking studies and assays involving DNA interaction via agarose gel electrophoresis and UV-Vis titration revealed no DNA interaction or inhibition of topoisomerase II alpha enzyme activity. However, these compounds demonstrated potent cytotoxic effects (IC50) against breast tumor (MCF-7) and prostate (DU-145) cell lines, as well as non-tumor prostate (PNT2) cell lines. These findings highlight the relevance of structural variations and the metallic center's nature in achieving cytotoxic effects, offering insights into the development of bioactive compounds. (AU)

• FAPESP's process: 17/15850-0 - X-ray diffraction as a tool in potential drug development
• Grantee: Eduardo Ernesto Castellano
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/06874-6 - Applications of technologies and synthetic methodologies developed under continuous flow conditions at LQBO-UFSCar for the preparation of molecules with biological activities and APIs
• Grantee: Kleber Thiago de Oliveira
• Support Opportunities: Regular Research Grants
• 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: 19/27176-8 - Asymmetric photocatalysis applied to the synthesis of Brivaracetam: synthetic approaches employing enabling technologies for chemical synthesis
• Grantee: Kleber Thiago de Oliveira
• 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