Synthesis of copper, silver and gold complexes involving nucleotide analogues in the search of new alternatives for the treatment of ovarian cancer

• Grant number: 21/08717-8
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2021 - October 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Pedro Paulo Corbi
• Grantee: Pedro Paulo Corbi
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Ovarian cancer is one of the most common in women. Depending on the patient's conditions, the treatment may include surgery, radiotherapy, immunotherapy and chemotherapy, the last one including platinum(II) complexes such as cisplatin. However, platinum drugs present limitations during treatment, such as development of resistance and adverse effects. For this reason, the search for new and improved antitumor drugs has experienced an extraordinary growth in the last decades, including the synthesis of new agents with less adverse effects. In this context, other transition metals, mainly from group 11 (copper, gold and silver), have been considered for the synthesis of new metal-based chemotherapeutics with antitumoral action, presenting a different spectrum of action when compared to platinum(II) drugs. Thus, this proposal aims to develop new metallopharmaceutical agents for the treatment of cancer with emphasis on the ovarian tumors. In order to achieve such objective, the synthesis and characterization of copper(II), silver(I) and gold(I)/(III) complexes with nucleotide analogs such as trifluridine, 5-(trifluoromethyl)uracil, 6-(trifluoromethyl)uracil, 5-fluorocitosin and 5-fluorouracil will be done, the latter being an antitumoral agent widely used in medical practice and explored in our group in recent years as a potential ligand. The characterization of the new compounds will be carried out by a set of chemical and spectroscopic analyses. Antiproliferative activity assays will be conducted to evaluate the activity of the compounds in different human tumor cell lines, with emphasis on the ovarian ones. The complexes that present the best in vitro activities will be subjected to biophysical assays with biomolecules of interest, such as DNA and proteins, to evaluate their possible biological targets. (AU)