In silico analysis of the inhibitory activities of novel azo derivatives of benzimidazole on egfr (her-2) kinase domain

Background: Epidermal growth factor receptors (EGFR) in human were involved in various types of cancers represented by abnormal signal transduction. This class consists of EGFR (ErbB1), HER2 (ErbB2, HER2), HER3 (ErbB3), and HER4 (ErbB4). Among them, EGFR and HER2 are related to breast cancer and are appropriate targets in dealing with various breast cancer cases. Disturbance of EGFR signalling, both by blocking EGFR binding sites or suppressing intracellular tyrosine kinase activity, can inhibit the rise of EGFR expressing tumours and recover the patient's condition. In this interest, a set of some new azo benzimidazole derivatives were prepared by coupling the diazonium derivative of benzimidazole with different suitable aromatic compounds and are used as ligands to dock against human HER2 kinase domain receptor. Materials and Methods: For this purpose, the crystal structure of the EGFR Kinase domain associated with TAK 285 (PDB ID: 3POZ, 1.5 Å X-ray resolution) was retrieved from the RCSB Protein Database (PDB) and used as the target. Results: All the compounds firmly inhibited by completely filling the active sites in the model with low energy values. Conclusion: Present study backed the in vitro activity of compounds designed by Mohanty et al., (4) and proved that the compounds of the current study inhibit the EGFR Kinase domain. So, these designed compounds can be used in drug development against some diseases that may somehow be related to the protein EGFR Kinase domain.