In Silico Analysis and Molecular Docking Studies of Novel 6,7-dihydropyrano [2,3-d] pyrimidin-5-one Derivatives as Human Epidermal Growth Factor Receptor 2 (HER2) and Epidermal Growth Factor Receptor (EGFR) Inhibitors

Background: HER2 is a member of the human epidermal growth factor receptor (HER/EGFR-/ERBB) family. Amplification or over-expression of this oncogene has been shown to play a major role in the development and progression of certain destructive types of breast cancer. Several drugs like Trastuzumab, Pertuzumab, Capecitabine, and Letrozole are used in the patients with metastatic breast cancer that overexpress the HER2 receptor. Materials and Methods: We aimed to investigate, the prevalence, ADME prediction, biological activity prediction of novel HER2/ EGFR mutations in breast cancer. Literature review shows that pyrano pyrimidin scaffold plays important role in the treatment of Brest cancer. So we have to design novel 6,7-Dihydropyrano [2,3-d] pyrimidin-5-one derivatives with virtual screening techniques. Molecular target prediction shows that all derivatives act on tyrosine kinase. Results: Among all the compounds H11 (-8.8 kcal/mol), H2 (-8.7 kcal/mol), H15 (-8.6 Kcal/mol), and H17 (-8.7 Kcal/mol) had a maximum binding affinity as compared to Cipecitabine (-6.0 kcal/mol), STD1 (-7.2 Kcal/mol) and STD2 (-7.9 Kcal/mol) and other derivatives. Most of the compounds are moderately active and do not cross the blood brain barrier. Conclusion: The bioactivity prediction shows that all compounds are active to moderately active. These positive results show that it could be further investigated and explored.