TY - JOUR ID - 90120 TI - Identification of oxazolo[4,5-g]quinazolin-2(1H)-one Derivatives as EGFR Inhibitors for Cancer Prevention JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Senthil, Renganthan AU - Meenakshi Sundaram, Kishore Kumar AU - Bupesh, Giridharan AU - Usha, Singaravelu AU - Saravanan, Konda Mani AD - Marudupandiyar College (Affiliated to Bharathidasan University), Thanjavur – 613403, Tamilnadu, India. AD - Department of Biotechnology, Bharath Institute of Higher Education and Research, Chennai – 600073, Tamilnadu, India. AD - Department of Forest Science, Nagaland University, Zunheboto, Nagaland -798627, India. AD - Department of Bioinformatics, Bharathiar University, Coimbatore - 641 046, Tamilnadu, India. Y1 - 2022 PY - 2022 VL - 23 IS - 5 SP - 1687 EP - 1697 KW - Tyrosine kinase KW - pharmacophore-based virtual screening KW - inhibitor discovery KW - cancer biology KW - drug discovery DO - 10.31557/APJCP.2022.23.5.1687 N2 - Objective: Abnormal expression of EGFR (epidermal growth factor receptor) results in different types of human tumors. Quinazoline-containing derivative signify an attractive platform for EGFR inhibitors. The present study aims to discover the potential binders of a group of compounds belonging to oxazolo[4,5-g]quinazoline-2(1H)-one derivative as EGFR inhibitors. Methods: We apply multiple computational procedures, including pharmacophore-based virtual screening methods, to perform a preliminary screening against EGFR over compounds belonging to oxazolo[4,5-g]quinazoline-2(1H)-one derivative. Then, we carried a fine screening by molecular dynamics simulations, followed by free energy calculations. Results: The best pharmacophore model created has five characteristics. Three hydrogen bonds acceptors (A) and two aromatic rings (R) make up AAARR (a sequential representation of chemical features of ligands). We have performed pharmacophore-based screening with different databases like Asinex, Chembridge, Lifechemicals, Maybridge, Specs, and Zinc. Top-scoring 30 molecules were considered for performing induced fit docking. Molecular Dynamics Simulations executed for the top five ligands confirmed that throughout the simulation, the protein-ligand complexes remained stable. Conclusion: Thus, the results obtained from this research provide insights for the development of oxazolo[4,5-g]quinazoline-2(1H)-one derivative as potent EGFR inhibitors. UR - https://journal.waocp.org/article_90120.html L1 - https://journal.waocp.org/article_90120_a103c982966fb64a6a9fe6b56ed1fc14.pdf ER -