In-silico identification of small molecule benzofuran-1,2,3-triazole hybrids as potential inhibitors targeting EGFR in lung cancer via ligand-based pharmacophore modeling and molecular docking studies.

Lung cancer is one of the most common and deadly types of cancer worldwide, and the epidermal growth factor receptor (EGFR) has emerged as a promising therapeutic target for the treatment of this disease. In this study, we designed a library of 1840 benzofuran-1,2,3-triazole hybrids and conducted pharmacophore-based screening to identify potential EGFR inhibitors. The 20 identified compounds were further evaluated using molecular docking and molecular dynamics simulations to understand their binding interactions with the EGFR receptor. In-silico ADME and toxicity studies were also performed to assess their drug-likeness and safety profiles. The results of this study showed the benzofuran-1,2,3-triazole hybrids BENZ-0454, BENZ-0143, BENZ-1292, BENZ-0335, BENZ-0332, and BENZ-1070 dock score of - 10.2, - 10, - 9.9, - 9.8, - 9.7, - 9.6, while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of the receptor, indicating their potential as inhibitors. The in-silico ADME and toxicity studies suggested that the compounds had good pharmacokinetic and safety profiles, further supporting their potential as therapeutic agents. Finally, performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of benzofuran-1,2,3-triazole hybrids as promising EGFR inhibitors for the treatment of lung cancer. Overall, this study provides a valuable starting point for the development of novel EGFR inhibitors with improved efficacy and safety profiles.

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Supplementary information: The online version contains supplementary material available at 10.1007/s40203-023-00157-1.