Oxadiazole derivatives as potential egfr protein kinase inhibitors: prediction of in-silico admet properties and molecular docking study

Background:Hepatocellular carcinoma is strongly linked to abnormalities in the EGFR triggers pathway, which is crucial for tumor cell growth, survival, and the formation of new blood vessels. This study investigates the potential of targeting EGFR-mediated pathways to inhibit tumor growth and progression, offering insights into the development of novel treatments for HCC. Methods: The methodology involves design of a virtual library of 1,3,4-oxadiazole derivatives, performing in-silico computational prediction, and conducting ADMET analysis property to evaluate the pharmacokinetic and toxicity profiles of the selected compounds. A molecular docking study was performed using 30 compounds on PDB ID: 1M17 with Molegro Virtual Docker to investigate the binding patterns of ligand molecules at their target site. Results: The drug likeness, Molinspiration and preADMET properties of 1,3,4-Oxadiazole designed derivatives have been found to be within the recommended acceptable range. Among all the derivatives, S10 and S23 exhibited the most impressive inhibitory potential against the EGFR receptor. The derivatives were observed with higher docking scores (-127.637 and -148.27) with Re-rank score(-98.405.11 and 117.52 kcal/mol) than the Co-crystallized ligand (Docking score -124.917; Re-rank score -93.688 kcal/mol). Compound S23 showing 4 H-bond interactions i.e. Met 769, Gln767, Thr766, Asp831 which is significant as compared to standard drug Afatinib having dock score of -134.695 and with 1 H-bond interactions i.e. Lys 721 Docking results proposed that these newly designed compounds might be used as EGFR inhibitors. Conclusion: This systematic screening provides a robust foundation for selecting and refining molecules with the best potential for therapeutic application, aligning with both scientific innovation and regulatory compliance.