Antitumor potential and toxicity of hybrid molecules of Chalcones and Quinazolines in uterine colon cancer cells.

• Grant number: 24/22260-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Renato José da Silva Oliveira
• Grantee: Maria Eduarda Souza Alves
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Cervical cancer is a serious public health issue in Brazil, often asymptomatic in its early stages and potentially invasive if left untreated. Current treatments cause side effects and face challenges related to drug resistance, highlighting the need for new therapeutic approaches. Chalcones have antineoplastic activity, while quinazolines act as tyrosine kinase inhibitors. Hybrid therapies, which combine two pharmacological structures into a single compound, have shown promise in treatment. Thus, the objective of this study is to evaluate the in vitro antitumor potential and toxicity of new hybrid molecules of chalcones and quinazolines in cervical cancer cell lines and non-tumor cell lines. The One-Dose Screening protocol will be used to select the best molecules. Cell lines will be treated with the compounds at various concentrations, and cytotoxicity will be assessed using SRB. The selected compounds will also be combined with each other and with chemotherapeutic agents (5-FU, cisplatin, and paclitaxel) to assess synergistic, additive, or antagonistic activity. Flow cytometry will evaluate cell death and the cell cycle, while western blotting will investigate the signaling pathways affected by the treatment. A three-dimensional tumor cell model will be used to validate the findings from the 2D model, in which spheroid cell viability, caspase activation, and morphology will be assessed. The goal is to identify promising drugs for the treatment of cervical cancer.