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
• Start date: November 01, 2021
• End date: 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)

Scientific publications

(8)

(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)

BERGAMINI, FERNANDO R. G.; NUNES, JULIA H. B.; MANZANO, CARLOS MARROTE; DE CARVALHO, MARCOS ALBERTO; RIBEIRO, MARCOS ANTONIO; RUIZ, ANA LUCIA TASCA GOIS; DE CARVALHO, JOAO ERNESTO; LUSTRI, WILTON ROGERIO; DE PAIVA, RAPHAEL ENOQUE FERRAZ; PORTES, MARCELO CECCONI; et al. Investigating the antiproliferative activities of new Cu-II complexes with pyridine hydrazone derivatives of nalidixic acid. Journal of Inorganic Biochemistry, v. 234, p. 11-pg., 2022-09-01. (21/08717-8, 13/07937-8, 18/12590-0, 17/25995-6, 15/25114-4, 18/12062-4)

SILVA, AMANDA A.; FRAJACOMO, SILMARA C. L.; CRUZ, ALLEFE B.; BUGLIO, KAIO EDUARDO; AFFONSO, DANIELE DAIANE; PORTES, MARCELO CECCONI; RUIZ, ANA LUCIA T. G.; DE CARVALHO, JOAO ERNESTO; LUSTRI, WILTON R.; PEREIRA, DOUGLAS H.; et al. Copper(II) and Platinum(II) Naproxenates: Insights on Synthesis, Characterization and Evaluation of Their Antiproliferative Activities. INORGANICS, v. 11, n. 8, p. 21-pg., 2023-08-01. (13/07937-8, 18/12062-4, 21/07458-9, 21/10265-8, 11/01114-4, 14/23950-7, 21/08717-8)

LUSTRI, WILTON R.; LAZARINI, SILMARA C.; AQUARONI, NAYARA AP SIMEI; RESENDE, FLAVIA A.; ALEIXO, NADIA A.; PEREIRA, DOUGLAS H.; LUSTRI, BRUNA CARDINALI; MOREIRA, CRISTIANO GALLINA; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; et al. A new complex of silver(I) with probenecid: Synthesis, characterization, and studies of antibacterial and extended spectrum beta-lactamases (ESBL) inhibition activities. Journal of Inorganic Biochemistry, v. 243, p. 12-pg., 2023-03-30. (18/00163-0, 19/03049-7, 15/09833-0, 15/20882-3, 18/12062-4, 17/16278-9, 21/07458-9, 17/19243-1, 20/13497-4, 18/12590-0, 19/26696-8, 18/00187-7, 21/08717-8, 18/02344-2)

OLIVEIRA, IGOR SANTOS; MANZANO, CARLOS MARROTE; NAKAHATA, DOUGLAS HIDEKI; SANTIAGO, MARIANA BRENTINI; SILVA, NAGELA BERNADELLI SOUSA; MARTINS, CARLOS HENRIQUE GOMES; RESPINDULA, FERNANDO PIMENTEL; PEREIRA, DOUGLAS HENRIQUE; CORBI, PEDRO PAULO. Antibacterial and antifungal activities in vitro of a novel silver(I) complex with sulfadoxine-salicylaldehyde Schiff base. Polyhedron, v. 225, p. 12-pg., 2022-08-04. (17/25995-6, 18/12062-4, 21/08717-8)

SILVA, RAPHAEL TRISTAO CRUVINEL; GUIDOTTI-TAKEUCHI, MICAELA; PEIXOTO, JESSICA LAURA MIRANDA; DEMARQUI, FERNANDA MANAIA; MORI, ANANDA PAULA; DUMONT, CAROLYNE FERREIRA; FERREIRA, GABRIELLA RAYANE APARECIDA; PEREIRA, GABRIELE DE MENEZES; ROSSI, DAISE APARECIDA; CORBI, PEDRO PAULO; et al. New Palladium(II) Complexes Containing Methyl Gallate and Octyl Gallate: Effect against Mycobacterium tuberculosis and Campylobacter jejuni. Molecules, v. 28, n. 9, p. 16-pg., 2023-05-05. (21/08717-8)

PEREIRA, GABRIELE DE MENEZES; NUNES, JULIA H. BORMIO; CRUZ, ALLEFE B.; PEREIRA, DOUGLAS HENRIQUE; BUGLIO, KAIO EDUARDO; RUIZ, ANA LUCIA T. G.; DE CARVALHO, JOAO ERNESTO; FRAJACOMO, SILMARA CRISTINA L.; LUSTRI, WILTON R.; BERGAMINI, FERNANDO R. G.; et al. Synthesis, spectroscopic characterization, antibacterial activity and antiproliferative profile of a new silver(I) complex of 5-fluorocytosine. JOURNAL OF FLUORINE CHEMISTRY, v. 266, p. 9-pg., 2023-02-01. (21/08717-8, 21/07458-9)

IGOR HENRIQUE CERQUEIRA; MARIA JULIA MIELI; ANNA KARLA DOS SANTOS PEREIRA; PEDRO PAULO CORBI; FLAVIA APARECIDA RESENDE. EVALUATION OF THE CYTOTOXICITY AND GENOTOXICOLOGICAL SAFETY PROFILE OF BIOACTIVE SILVER(I) COMPLEXES WITH AMINOADAMANTANE LIGANDS. Química Nova, v. 47, n. 6, 2024-03-11. (21/08717-8, 17/16278-9, 21/10265-8)

NUNES, JULIA HELENA BORMIO; NAKAHATA, DOUGLAS HIDEKI; CORBI, PEDRO PAULO; PAIVA, RAPHAEL ENOQUE FERRAZ DE. Beyond silver sulfadiazine: A dive into more than 50 years of research and development on metal complexes of sulfonamides in medicinal inorganic chemistry. Coordination Chemistry Reviews, v. 490, p. 45-pg., 2023-05-22. (21/10265-8, 21/08717-8)