Abstract
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.
Highlights
Molecular dockingCancer is a category of diseases involving irregular cell growth that have the ability to invade or spread to other areas of the body and it’s the second most deadly in terms of morbidity and mortality
The various molecular targets explored in cancer therapeutics includes tyrosine kinase, proteasome, histone deacetylase (HDAC), thymidine phosphorylase, cyclin-dependent kinase (CDK), aurora kinase, mTOR, STAT proteins, ETS proteins, PLK-1 and SCF protein
Tyrosine kinases are mainly classified as receptor tyrosine kinase (RTK) e.g. EGFR, PDGFR, FGFR, IR, ALK and non-receptor tyrosine kinase (NRTK) e.g. SRC, ABL, FAK, and Janus kinase
Summary
Cancer is a category of diseases involving irregular cell growth that have the ability to invade or spread to other areas of the body and it’s the second most deadly in terms of morbidity and mortality. The various molecular targets explored in cancer therapeutics includes tyrosine kinase, proteasome, histone deacetylase (HDAC), thymidine phosphorylase, cyclin-dependent kinase (CDK), aurora kinase, mTOR, STAT proteins, ETS proteins, PLK-1 and SCF protein. Tyrosine kinases are mainly classified as receptor tyrosine kinase (RTK) e.g. EGFR, PDGFR, FGFR, IR, ALK and non-receptor tyrosine kinase (NRTK) e.g. SRC, ABL, FAK, and Janus kinase. There are currently only 12 small molecule FAK inhibitors in different phases of clinical trials, with no marketed molecule till date and there is scope to increase this armamentarium of anti-cancer drugs by identifying promising leads
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
