Evaluation of the biological profile of coordination complexes: an approach in 2D and 3D cell models

• Grant number: 22/02876-0
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2022 - July 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Fillipe Vieira Rocha
• Grantee: Fillipe Vieira Rocha
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated researchers: Martin Nielsen Bayer ; Vivian Capilla-González
• Associated grant(s): 23/14800-0 - Metabolic Activity and Cell Proliferation evaluation of coordination compounds in 3D Bioprinted Ovarian Tumor Model, AP.R SPRINT

Abstract

In vitro cell cultures are fundamental techniques in developing new drug candidates. Traditional cell culture methods use a two-dimensional (2D) monolayer. Today, this method has become standard technology in the life sciences, making continuous improvements. However, due to the inherent flaws of traditional 2D culture, this methodology cannot correctly mimic the architecture and microenvironments of the human organism. This limitation makes 2D cultured cells different from cells that grow in vivo in terms of morphology, proliferation, cellular and matrix interactions, differentiation, among other aspects. As a result of these conditions, about 95% of new anticancer candidates fail clinical trials despite robust indications of activity in preclinical in vitro models. Thus, the continuous development of tumor cell culture techniques is vital. In this context, 3D cultures models (spheroids and organoids) bring a new perspective to understanding the in vitro biological profile. Both generate physiologically relevant results since these models can simulate the main features of an in vivo environment, including cell-cell and cell-extracellular matrix interactions. They possibly lead to better screening and success of promising candidates in vivo and clinical trials. The research group Coordinating Compounds in Medicinal Chemistry (CCQM) has been specializing in investigating the mechanism of action of biologically active complexes in the combat against cancer. However, our data are limited to information from monolayer assays. Therefore, this project proposes the synthesis and evaluation of the behavior of several coordination compounds, including metalloporphyrin compounds, Pd(II), Ru(II), Ir(III), Eu(III), and Tb(III) complexes. All the compounds will be tested against tumor and non-tumor cell lines. The most promising compounds will be analyzed in a more representative biological environment through 3D cell culture (spheroids and organoids). Additionally, such complexes will have their biological action profile evaluated through cell morphology, cytotoxicity/cytostatic, cell cycle influence, and cell death mechanism assays. In addition, interaction studies against biomolecules (DNA, DNA-topoisomerases, and HSA) will be carried out by different techniques. These studies will bring a new horizon in the design and understanding of the mode of action of coordination compounds with possible antitumor action. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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; et al. Palladium (II) complexes as inhibitors of cathepsin B and topoisomerase I beta: Synthesis, characterization, and cytotoxicity. Journal of Molecular Structure, v. 1294, p. 14-pg., 2023-12-15. (19/11242-1, 21/04876-4, 22/02876-0)

CORDEIRO JUNIOR, PAULO JORGE MARQUES; SOUTO, ROBSON SILVA; ALMEIDA, MICHELL DE OLIVEIRA; PEREIRA, GEORGE BUENO SANTANA; FRANCO, MARIANE ARAUJO; HONORIO, KATHIA MARIA; ROCHA, FILLIPE VIEIRA; LANZA, MARCOS ROBERTO DE VASCONCELOS. A combined approach toward enhancing 2-electron oxygen reduction through the incorporation of Pd-based complex into a carbonaceous matrix: Experimental and mechanistic-theoretical studies. Electrochimica Acta, v. 460, p. 13-pg., 2023-05-20. (16/19612-4, 14/50945-4, 18/19103-8, 19/11242-1, 17/10118-0, 22/02876-0)