肺癌是一种复杂和异质性的疾病，其与包括表皮生长因子受体（EGFR）的过表达和突变在内的多种分子改变相关。本研究设计了一个含有1843个苯并咪唑-1,2,3-三唑混合物的文库，并进行了基于药效团的筛选，以鉴定潜在的EGFR抑制剂。进一步使用分子对接和分子动力学模拟评估了164个化合物与受体之间的结合相互作用。还进行了体外ADME和毒性研究，以评估所发现化合物的药物样性和安全性。本研究的结果表明，苯并咪唑-1,2,3-三唑混合物BENZI-0660、BENZI-0125、BENZI-0279、BENZI-0415、BENZI-0437和BENZI-1110对EGFR（PDB ID：4HJO）的对接得分分别为-9.7、-9.6、-9.6、-9.6、-9.6和-9.6，与参考分子-7.9 kcal/mol相比。分子对接和分子动力学模拟显示所发现化合物与EGFR的活性位点形成了稳定的相互作用，说明它们作为抑制剂的潜力。体外ADME和毒性研究显示这些化合物具有良好的药物样性和低毒性，进一步支持它们作为治疗剂的潜力。最后，对最佳选择的配体进行了DFT研究，以深入了解其电子性质。本研究的发现对苯并咪唑-1,2,3-三唑混合物作为潜在EGFR抑制剂治疗肺癌的潜力提供了重要见解。这项研究为发现和开发强效和选择性的EGFR抑制剂治疗肺癌开辟了一条新途径。

Lung cancer is a complex and heterogeneous disease, which has been associated with various molecular alterations, including the overexpression and mutations of the epidermal growth factor receptor (EGFR). In this study, designed a library of 1843 benzimidazole-1,2,3-triazole hybrids and carried out pharmacophore-based screening to identify potential EGFR inhibitors. The 164 compounds were further evaluated using molecular docking and molecular dynamics simulations to understand the binding interactions between the compounds and the receptor. In-si-lico ADME and toxicity studies were also conducted to assess the drug-likeness and safety of the identified compounds. The results of this study indicate that benzimidazole-1,2,3-triazole hybrids BENZI-0660, BENZI-0125, BENZI-0279, BENZI-0415, BENZI-0437, and BENZI-1110 exhibit dock scores of -9.7, -9.6, -9.6, -9.6, -9.6, -9.6 while referencing 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 EGFR, indicating their potential as inhibitors. The in-silico ADME and toxicity studies showed that the compounds had favorable drug-likeness properties and low toxicity, 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 benzimidazole-1,2,3-triazole hybrids as promising EGFR inhibitors for the treatment of lung cancer. This research opens up a new avenue for the discovery and development of potent and selective EGFR inhibitors for the treatment of lung cancer.Communicated by Ramaswamy H. Sarma.