Scholarship 24/21108-9 - - BV FAPESP
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Metal complexes and nucleobase analogs: a proposal for the treatment of skin squamous cell carcinoma

Grant number: 24/21108-9
Support Opportunities:Scholarships abroad - Research Internship - Master's degree
Start date until: February 20, 2025
End date until: July 30, 2025
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Pedro Paulo Corbi
Grantee:Francisco Mastrobuono Cordeiro de Almeida
Supervisor: Raphael Enoque Ferraz de Paiva
Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Institution abroad: Donostia International Physics Center, Spain  
Associated to the scholarship:23/11857-1 - Metal complexes and nucleotide analogs: a proposal for the treatment of skin squamous cell carcinomas, BP.MS

Abstract

Nucleobases are molecules considered as basic building blocks of DNA and RNA nucleic acids. When some part is chemically modified, they become known as nucleobase analogues, such as 2-thiouracil (2TU), 2,4-dithiouracil (2,4DTU) and 6-trifluorometiluracil (6-TFMU). Recent studies showed that when coordinated to metal ions like copper(II) and silver(II), their antitumoral, antiviral and antibacterial properties can be enhanced, which motivates further studies of such metal complexes with nucleobase analogues.Skin squamous cell carcinoma (SSCC) is one of the most prevalent tumors in humans and the second most common type of skin cancer. Currently, treatments are very limited to the use of mainly surgical resection, radiotherapy and chemotherapy but with limited effects. With this in mind, silver and copper complexes with 2TU, 2,4DTU and 6TFMU nucleobase analogues were synthesized and characterized in the first part of this project. The antiproliferative activities of the complexes were tested against six tumor cell lines. Both complexes were active over tumor cells, the silver complex with 2TU being the most active, including pharyngeal (FaDu) and tongue (SCC-25) cell carcinomas.In this context, this project seeks to explore the mechanisms of action of the free nucleobases and the silver(I) and copper(II) complexes prepared by conducting targeted biophysical assays and theoretical (molecular docking) studies to assess their interactions with specific biological targets. This part of the project shall take place at the Donostia International Physics Center in San Sebastián, under the supervision of Dr. Raphael Enoque Ferraz de Paiva.

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