Synthesis, characterization and antiproliferative and cytotoxic activities of Zn(II) complexes with nucleobases derivatives

• Grant number: 25/01640-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Pedro Paulo Corbi
• Grantee: Lucas Zanoni Davoli
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The growing incidence of cancer, as well as its greater resistance to traditional treatments, such as the use of cisplatin, has given great relevance to the search of new forms of treatment for this disease. The modification of existing drugs to increase their efficiency, as well as their combination with other active species, have shown to be effective methods and reported in the literature for this purpose. Among the most promising methods recently used is the combination of existing drugs with metals, which can lead to new efficient molecules against a group of tumor cells or the reduction of tumor resistance to the original drug. Nucleobases have been widely used in cancer treatment for years due to their intracellular importance, participating in processes of RNA and DNA synthesis and epigenetic signaling, thus being potent antimetabolites that can prevent cell replication and induce apoptosis. Zinc, in turn, is an essential trace element for the functioning of many proteins and enzymes, including relevance in the process of cell duplication and DNA repair. Furthermore, Zn²¿ metal complexes have been reported as potential cytotoxic agents on tumor cells. Therefore, this project aims to synthesize Zn2+ complexes with the nucleobase derivatives 5-fluorouracil and 5-fluorocytosine, characterizing them and evaluating their antitumor activity. The complexes will be prepared from aqueous solutions or in organic solvents such as methanol from the aforementioned nucleobases and zinc chloride and, subsequently, characterized regarding their compositions and structures by chemical and spectroscopic analyses. Antiproliferative activity assays will be performed on a panel of human tumor cell lines and one non-tumor cell line, using a colorimetric assay (MTT, sulforhodamine B). The results will be compared to commercial drugs, especially metallopharmaceuticals such as cisplatin and carboplatin, as well as other drugs used in clinical medicine.