Computational modelling and analysis of Pyrimidine analogues as EGFR inhibitor in search of anticancer agents

Introduction and Aim:Epidermal Growth Factor Receptor tyrosine kinase is a well-known widely studied cancer therapeutic target protein. Based on the reported anticancer activity of pyrimidines, series 13 compounds are designed. In present studythe EGFR domain targeted with designed compounds.
 Materials Methods:With missing residue in crystallized structure, modelled using homology modelling, evaluated, energy-based optimization carried out OPLS Gromacs. The default bindingsite was considered from known – Erlotinibcomplex structure. molecular docking AutodockVina, Insilico toxicity profiling enrichment analysis pathway Swiss-ADME Enrich R.
 
 Results:Compounds 7, 9, 10 12 revealed binding energy -8.8, -8.3, -8.3 -8.4 Kcal/mol makes two h-bonds MET-769. All under range Lipnski drug likeness, high GI-absorption rate. Considering metabolic enzyme activity, entire predicted to inhibit metabolizing CYP1A2, CYP2D6 CYP3A4. Compounds 2, 3, 8 acts as substrate CYP2C19 compound 1, 3,4, 5, 6, 8, 10, 11, act CYP2C9.
 Conclusion:The inhibition may affect poor slowing down excretion time molecules body. current in-silico docking, PKPD study suggesting that they can be developed putative lead for developing new anti-cancer drugs.