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


  • PurraBuchi Reddy
  • M.B Madhusudana Reddy
  • . Ramakrishna Reddy
  • Santosh S. Chhajed
  • Pramodkumar P. Gupta



Pyrimidines, PKPD, molecular docking, toxicity prediction


Introduction and Aim:Epidermal Growth Factor Receptor tyrosine kinase is a well-known and widely studied cancer therapeutic target protein. Based on the reported anticancer activity of pyrimidines, a series of 13 compounds are designed. In the present studythe EGFR kinase domain is targeted with the designed 13 compounds.

Materials and Methods:With missing residue in the kinase domain of EGFR crystallized structure, the domain is modelled using homology modelling, evaluated, energy-based optimization is carried out using OPLS in Gromacs. The default bindingsite was considered from the known EGFR kinase domain – Erlotinibcomplex crystallized structure. The molecular docking is carried out using AutodockVina, Insilico toxicity profiling and enrichment analysis of pathway is studied using Swiss-ADME and Enrich R.


Results:Compounds 7, 9, 10 and 12 revealed a binding energy of -8.8, -8.3, -8.3 and -8.4 Kcal/mol and makes two h-bonds with MET-769. All the 13 compounds are under the range of Lipnski drug likeness, with high GI-absorption rate. Considering the metabolic enzyme activity, the entire series of compounds are predicted to inhibit the metabolizing enzyme CYP1A2, CYP2D6 and CYP3A4. Compounds 2, 3, 7, 8 and 13 acts as a substrate to CYP2C19 and compound 1, 3,4, 5, 6, 7, 8, 9, 10, 11, 12 and 13 act as a substrate to CYP2C9.

Conclusion:The inhibition of metabolizing enzyme may affect the poor metabolizing and slowing down the excretion time of molecules from the body. The current in-silico molecular docking, in-silico PKPD study of compounds suggesting that they can be developed as putative lead compounds for developing new anti-cancer drugs.

Author Biographies

PurraBuchi Reddy

Department of Chemistry, REVA University, Bangalore, Karnataka, India

M.B Madhusudana Reddy

Department of Chemistry, REVA University, Bangalore, Karnataka, India

. Ramakrishna Reddy

Department of Chemistry, REVA University, Bangalore, Karnataka, India

Santosh S. Chhajed

Department of Pharmaceutical Chemistry, MET’s Institute of Pharmacy, Nashik, Maharashtra, India

Pramodkumar P. Gupta

School of Biotechnology and Bioinformatics, D Y Patil Deemed to be University, Navi Mumbai, Maharashtra, India


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How to Cite

Reddy P, Madhusudana Reddy M, Reddy . R, Chhajed SS, Gupta PP. Computational modelling and analysis of Pyrimidine analogues as EGFR inhibitor in search of anticancer agents. Biomedicine [Internet]. 2021Apr.3 [cited 2021Apr.14];41(1):130-8. Available from:



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