Computational Evaluation of Bioactive Compounds from Colocasia affinis Schott as a Novel EGFR Inhibitor for Cancer Treatment

Introduction: Epidermal growth factor receptor (EGFR) is a transmembrane protein that belongs to the ErbB/HER-family of tyrosine kinase receptors. Somatic mutations and overexpression of EGFR have been reported to play a vital role in cancer cell development and progression, including cell proliferation, differentiation, angiogenesis, apoptosis, and metastatic spread. Hence, EGFR is an important therapeutic target for the treatment of various types of epithelial cancers. Somatic mutations have led to resistance to clinically approved synthetic EGFR inhibitors. Furthermore, synthetic EGFR inhibitors have been associated with several side effects. Thus, there is a need to develop novel EGFR inhibitors with an acceptable biosafety profile and high efficacy. Methods: Herein, we employed structural bioinformatics and theoretical chemistry techniques via molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) calculation, density functional theory analysis (DFT), and pharmacokinetic study to identify novel EGFR inhibitors. Results: The stringent molecular docking and MM-GBSA calculations identified MET 793, LYS 745, PHE 723, ASP 855, ARG 411, and THR 854 as principal amino acid residues for EGFR-ligands interactions. Furthermore, Colocasia affinis Schott compounds exhibited higher binding energy and more stable interactions than the reference compound (gefitinib). DFT analysis also ascertains better bioactivity and chemical reactivity of C. affinis Schott with favorable intramolecular charge transfer between electron-donor and electron acceptor groups. The pharmacokinetic profile of C. affinis Schott bioactive compounds satisfies Lipinski’s rule of five assessment. Conclusion: Collectively, C. affinis Schott compounds demonstrated higher inhibitory potentials against EGFR and better pharmacological properties when compared with gefitinib. C. affinis Schott compounds are therefore suggested as promising therapeutic EGFR inhibitors for cancer treatment.