肺癌是一个重大的全球公共卫生问题，也是癌症相关死亡的主要原因。有几种药物通常用于治疗肺癌，可以单独使用，也可以与其他治疗方法联合使用。间变性淋巴瘤激酶 (ALK) 蛋白是被认为是肺癌潜在治疗靶点的几种靶蛋白之一。已鉴定出多种 ALK 抑制剂，但其中许多都与副作用和毒性问题有关。在本研究中，我们打算通过计算预测葫芦素 (CBN)、A 和 B 与 ALK 活性口袋的结合潜力，以估计其潜在的 ALK 抑制剂。与结合能为-7.9kcal/mol的CBN-A相比，CBN B的结合能明显更好，结合能为-8.1kcal/mol。这与克唑替尼的结合能为-8.2kcal/mol 非常接近。分子动力学模拟的结果表明，对接的复合物在 100 ns 模拟期间保持稳定。 CBN 以剂量依赖性方式抑制非小细胞肺癌细胞系 H1299 和 A549 的增殖。 CBN-B 抑制肺癌细胞的增殖，对 H1299 细胞的 IC50 值为 0.08μM，对 A549 细胞的 IC50 值为 0.10μM。计算分析提供了强有力的证据，表明 CBN-B 有潜力作为 ALK 的有效天然抑制剂，并可能被证明是肺癌的一种有价值的治疗选择。由 Ramaswamy H. Sarma 传达。

Lung cancer is a major global public health issue and the leading cause of cancer-related deaths. Several medications are commonly used to treat lung cancer, either alone or in combination with other treatments. The anaplastic lymphoma kinase (ALK) protein is one of several target proteins that are thought to be potential therapeutic targets in the context of lung cancer. Several ALK inhibitors have been identified, but many of these have been associated with side effects and toxicity concerns. In this study, we intend to computationally predict the binding potential of cucurbitacins (CBNs), A and B to the active pockets of ALK, in order to estimate their potential ALK inhibitors. Compared to CBN-A, which has a binding energy of -7.9 kcal/mol, CBN B exhibits significantly better binding efficacy with a binding energy of -8.1 kcal/mol. This is closely comparable to the binding energy of Crizotinib, which is -8.2 kcal/mol. The results of the molecular dynamics simulation indicated that the docked complexes remained stable for the duration of the 100 ns simulation period. CBN inhibited the proliferation of both non-small cell lung cancer cell lines, H1299 and A549, in a dose-dependent manner. CBN-B inhibited the proliferation of lung cancer cells, showing IC50 values of 0.08 µM for H1299 cells and 0.10 µM for A549 cells. The computational analyses provide strong evidence that CBN-B has the potential to act as a potent natural inhibitor against ALK, and could prove to be a valuable treatment option for lung cancer.Communicated by Ramaswamy H. Sarma.