Lung cancer is a disease in which lung cells grow abnormally and uncontrollably, and the cause of it is direct smoking, secondhand smoke, radon, asbestos, and certain chemicals. The worldwide leading cause of death is lung cancer, which is responsible for more than 1.8 million deaths yearly and is expected to rise to 2.2 million by 2030. The most common type of lung cancer is non-small cell lung cancer (NSCLC), which accounts for about 80% and small cell lung cancer (SCLC), which is more aggressive than NSCLC and is often diagnosed later and accounts for 20% of cases. The global concern for lung cancer demands efficient drugs with the slightest chance of developing resistance, and the idea of multitargeted drug designing came up with the solution. In this study, we have performed multitargeted molecular docking studies of Drug Bank compounds with HTVS, SP and XP algorithms followed by MM\GBSA against the four proteins of lung cancer cellular survival and stress responses, which revealed Mitoglitazone as a multitargeted inhibitor with a docking and MM\GBSA score ranging from − 5.784 to − 7.739 kcal/mol and − 25.81 to − 47.65kcal/mol, respectively. Moreover, we performed pharmacokinetics studies and QM-based DFT analysis, showing suitable candidate and interaction pattern analysis revealed the most count of interacting residues was 4GLY, 5PHE, 6ASP, 6GLU, 6LYS, and 6THR. Further, the results were validated with SPC water model-based MD simulation for 100ns in neutralised condition, showing the cumulative deviation and fluctuation < 2Å with many intermolecular interactions. The whole analysis has suggested that Mitoglitazone can be used as a multitargeted inhibitor against lung cancer—however, experimental studies are needed before human use.

肺癌是一种肺细胞异常且不受控制地生长的疾病，其病因是直接吸烟、二手烟、氡气、石棉和某些化学物质。全球最主要的死亡原因是肺癌，每年导致超过 180 万人死亡，预计到 2030 年将增至 220 万人。最常见的肺癌类型是非小细胞肺癌 (NSCLC)，约占 80%，小细胞肺癌 (SCLC) 比 NSCLC 更具侵袭性，通常诊断较晚，占病例的 20%。全球对肺癌的关注需要有效的药物，且产生耐药性的可能性最小，多靶点药物设计的想法提出了解决方案。在本研究中，我们使用 HTVS、SP 和 XP 算法对药物库化合物进行了多靶点分子对接研究，然后使用 MM\GBSA 针对肺癌细胞存活和应激反应的四种蛋白质进行了多靶点分子对接研究，结果表明米托格列酮是一种具有对接的多靶点抑制剂MM\GBSA 得分范围分别为 − 5.784 至 − 7.739 kcal/mol 和 − 25.81 至 − 47.65 kcal/mol。此外，我们进行了药代动力学研究和基于 QM 的 DFT 分析，显示了合适的候选者，相互作用模式分析显示相互作用残基数量最多的是 4GLY、5PHE、6ASP、6GLU、6LYS 和 6THR。此外，结果通过基于 SPC 水模型的 MD 模拟在中和条件下进行了 100 纳秒的验证，显示了许多分子间相互作用的累积偏差和波动 < 2Å。整个分析表明，米托格列酮可以用作肺癌的多靶点抑制剂——然而，在人类使用之前还需要进行实验研究。