Use, encapsulation, cellular action mechanism, and activity in 3D culture of copper complexes using cinnamaldehyde imine derivatives: studies for potential new agents for brain tumors.

• Grant number: 23/12127-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2024
• Effective date (End): May 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Giselle Cerchiaro
• Grantee: Rafael Nunes Gomes
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Copper complexes are an alternative therapy or co-therapy against neoplasms. Given its very versatile redox capacity among the elements of the first transition series, copper can assume the most different forms and coordination geometries and consequently its high reactivity can be controlled in this way. Thus, being an endogenous element, whose cells have full regulatory and transport capacity, and having a redox activity that can be controlled, copper can be used as a potential drug against cancer cells. After the discovery of the cell death mechanism induced by copper (cuproptosis) at the end of 2022 by Tsvetkov and collaborators, the scientific community is in the process of unraveling its intricacies. Highlighting that the discovery of the cuproptosis mechanism provides a direction for future research on copper formulations that can induce cell death and may have some application advantages in future aspects, in the treatment of cancer and in treatment strategies to overcome resistance to current drugs. . The correlation between cuproptosis and cancer needs further exploration, emphasizing the importance of studies that focus on targeting copper in cancer therapy having the potential for the development of new therapeutic strategies that can improve cancer treatment. In this context, the current project seeks to understand in depth the mechanisms of action of copper (II) complexes with imine ligands derived from cinnamaldehyde, in glioblastoma and neuroblastoma cell lines, 3D cell culture models of spheroids and cerebral organoid models, constructed with pluripotent cells. Investigating the ability of these complexes to alter the cell cycle, compromise genomic stability, alter copper homeostasis and cause the expression of proteins linked to apoptosis and DNA repair. Furthermore, we aim to develop more stable formulations using the encapsulation of the complexes in liposome nanostructures in order to enhance the effects of copper compounds.