Synthesis of kinase inhibitors as anti-cancer agents

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase located at the extracellular matrix cell adhesion site. This kinase mediates downstream signalling cascades on the cell-extracellular matrix of integrins, cytokine receptors, growth factor receptors and G-protein-coupled receptors. Several studies have suggested the importance of FAK in cancer cell adhesion, motility, proliferation and survival and is over-expressed in cancer cells. Herein, we report a series quinazolinone-amine analogues (4a-4j) synthesized using conventional and microwave methods. These synthesized analogues were evaluated using MTT assay on MCF-7 and MDA-MB-231 cell lines indicated that analogues have potent cytotoxicity activity. The molecular docking studies on FAK showed that 4h and 4i have maximum binding affinity of -8.9 kcal/mol. This could be attributed to the presence of fluoro (-F) and nitro (-NO₂) group. This research work demonstrated the utility of quinazolinone series as potential FAK inhibitors. Analogue 4h emerged as a strong lead that can be developed into a potent FAK inhibitor in cancer therapeutics.