Synthesis, characterization and use in brain tumor cell cultures of new copper (II) complexes with phytochemical ligands

Abstract

Copper complexes are currently 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. Based on this knowledge, the present project aims to synthesize, characterize and encapsulate new copper complexes that will be used for in vitro testing of brain tumors. To this end, new antitumor therapies will be tested using unprecedented copper (II) complexes prepared from ligands derived from plant metabolites. The desired complexes will be synthesized through direct coordination, characterized by spectroscopic techniques - EPR, UV-Vis, Infrared and ESI-MS - and tests will be carried out to analyze cytotoxicity through traditional routes and through 3D cultures. The evaluation of the mechanism for reversing tumor cell proliferation of the complexes will be carried out through the level of expression of intra and extracellular proteins involved in cancer, and their signaling. It will also be evaluated how the compounds prevent growth in vitro, based on their action in the tumor microenvironment. To achieve this, the complexes will be encapsulated using liposomes, and their bioavailability will be analyzed using organ-in-a-chip models. (AU)