Glioblastoma is a highly aggressive and malignant type of brain tumor. It is the most common primary brain tumor in adults and is known for its rapid growth and resistance to treatment. Quinazoline derivatives are promising lead compounds that can be optimized for a variety of receptors leading to the discovery of novel ligands. The synthetic flexibility of quinazolinones enabled the synthesis of structurally diverse quinazoline derivatives with a wide range of pharmacological actions including anticancer. Although two dimensional (2D) monolayer cell culture models are well established protocols to study the cytotoxicity of compounds, 3D cell culture reflects the in vivo tumor complexity better, and can help bridge the gap between in vitro cell cultures and in vivo responses. In this study, novel synthesized 2,3-dihydroquinazolin-4(1H)-one derivatives will be investigated for their antiproliferative effect using 2D and 3D cell cultures models of glioblastoma. Additionally, mass spectrometry-based metabolomics approach will be used to give in depth understanding of the molecular mechanisms underlying the cytotoxicity of the compounds, highlight any differences between treated 2D and 3D glioblastoma cell cultures metabolome, and identify potential therapeutic targets.
The Project is Funded by The Deanship of Scientific Research/The University of Jordan (JD 20000)