非小细胞肺癌（NSCLC）是肺癌中最常见的类型，由于其高转移率而与不良预后相关。因此，寻找具有有效抗癌活性的新药物对于改善该疾病的临床结果至关重要。海洋生物展示了一种多样的具有抗癌效果的生物活性化合物的来源。报道了来自泰国蓝绵（Xestospongia sp.）的jorunnamycin A（JA）及其半合成衍生物22-(4'-pyridinecarbonyl) jorunnamycin A (22-(4'-py)-JA)的抗癌效应。本研究旨在采用体外、体内和体外模拟的方法研究22-(4'-py)-JA 对 NSCLC 转移的影响。JA衍生物抑制了人脐静脉内皮细胞（HUVECs）的肿瘤细胞侵袭和管形成。计算分析显示22-(4'-py)-JA与AKT蛋白之间的交互作用强而稳定。进一步对分子机制的研究表明，22-(4'-py)-JA通过抑制AKT/mTOR/p70S6K信号通路降低了基质金属蛋白酶（MMP-2和MMP-9）、缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的表达。此外，22-(4'-py)-JA通过减少肺部结节数抑制了体内转移。这些发现表明了22-(4'-py)-JA的抗转移活性，可能在进一步的临床应用中具有用途。© 2023美国化学学会。

Non-small-cell lung cancer (NSCLC), the most prevalent form of lung cancer, is associated with an unfavorable prognosis owing to its high rate of metastasis. Thus, the identification of new drugs with potent anticancer activities is essential to improve the clinical outcome of this disease. Marine organisms exhibit a diverse source of biologically active compounds with anticancer effects. The anticancer effects of jorunnamycin A (JA) derived from the Thai blue sponge (Xestospongia sp.) and 22-(4'-pyridinecarbonyl) jorunnamycin A (22-(4'-py)-JA), the semisynthetic derivative of JA, have been reported. The present study aimed to investigate the impact of 22-(4'-py)-JA on NSCLC metastasis using in vitro, in vivo, and in silico approaches. The JA derivative inhibited tumor cell invasion and tube formation in human umbilical vein endothelial cells (HUVECs). The computational analysis demonstrated strong and stable interactions between 22-(4'-py)-JA and the AKT protein. Further examinations into the molecular mechanisms revealed the suppression of AKT/mTOR/p70S6K signaling by 22-(4'-py)-JA, leading to the downregulation of matrix metalloproteinases (MMP-2 and MMP-9), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF). Furthermore, 22-(4'-py)-JA suppressed in vivo metastasis by decreasing the number of colonies in the lung. These findings indicated the antimetastasis activity of 22-(4'-py)-JA, which might prove useful for further clinical applications.© 2023 American Chemical Society.