Avaliação do efeito antitumoral de derivados de Quinazolinas em células de Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is a highly invasive and aggressive brain tumor. Classified as grade 4 malignancy, it is one of the most lethal tumors, with an average survival of 10 to 20 months after diagnosis. GBM does not respond well to conventional treatments, making the search for new therapeutic approaches crucial. In this context, our research group has been investigating the activity of quinazoline-derived compounds, molecules known for their biological properties, such as antitumor, antihypertensive, anti-inflammatory activity, kinase inhibition, among others. The general objective of this study was to evaluate the antitumor effect of KDY23, a quinazoline derivative, on GBM cells. The organic synthesis and physicochemical characterization of the synthesized molecules were performed, followed by biological assays. After treatment with the synthesized molecules, named KDYs, KDY23 significantly reduced the viability of GBM cells at concentrations starting from 10 µM, standing out as the most promising molecule. Through western blotting assays, the expression of cleaved caspase-3 and cleaved PARP proteins was observed in the cells treated with KDY23, indicating that the compound promotes cell death by apoptosis. To understand the mechanism of action of KDY23, qRT-PCR assays were performed, revealing that the compound acts on the survival and cell proliferation pathway known as the EGFR-PI3K/AKT1/mTOR pathway. The results suggest that KDY23 could be a potential candidate for the development of new therapies against GBM.