Enhanced expression of NADPH oxidase (NOX) and the subsequent production of reactive oxygen species (ROS) are associated with lung cancer. In the present study, fifty 6-amino-2,4,5-trimethylpyridin-3-ol derivatives were screened for anticancer activity by targeting NOX2-derived ROS. The compounds suppressed ROS production and decreased cancer cell viability (R² = 0.79). Among the derivatives, the compound coded BJ-1207, which contained a 4-(hydroxydiphenylmethyl)piperidine moiety, exhibited the most effective anticancer activity against A549 lung cancer cell line and eight other cancer cell lines, including H1299, MCF-7, MDA-MB-231, HT-29, SW620, Mia PaCa-2, PANC-1, and U937. BJ-1207 also showed significantly lower inhibitory effects on kinase insert domain receptor (KDR) and c-KIT tyrosine kinase but higher inhibitory activity on NOX than those of sunitinib, a multi-receptor tyrosine kinase (RTK) inhibitor. In addition, BJ-1207-induced inhibition of RTK-downstream signaling pathways, such as ROS production, and expression of target genes, such as stem cell factor and transforming growth factor-α, were similar to those induced by sunitinib. In the xenograft chick tumor model, BJ-1207 inhibited lung tumor growth to a similar or much greater extent than that of sunitinib or cisplatin, respectively. Overall, the present study showed that BJ-1207, a vitamin B₆-derived 2,4,5-trimethylpyridin-3-ol compound with azacyclonol moiety at C (6)-position of the pyridine ring, inhibited NOX activity and that it is a promising lead compound for developing anticancer drugs against lung cancer.

NADPH氧化酶（NOX）的增强表达和随后的活性氧（ROS）的产生与肺癌有关。在本研究中，通过靶向NOX2衍生的ROS，筛选了五十种6-氨基-2,4,5-三甲基吡啶-3-醇衍生物的抗癌活性。这些化合物抑制了ROS的产生并降低了癌细胞的活力（R ² = 0.79）。在这些衍生物中，编码为BJ-1207的化合物含有4-（羟基二苯甲基）哌啶部分，对A549肺癌细胞系和其他八种癌细胞系，包括H1299，MCF-7，MDA- MB-231，HT-29，SW620，Mia PaCa-2，PANC-1和U937。BJ-1207还显示出对激酶插入结构域受体（KDR）和c-KIT酪氨酸激酶的抑制作用显着降低，但对NOX的抑制活性高于多受体酪氨酸激酶（RTK）抑制剂舒尼替尼。此外，BJ-1207诱导的RTK下游信号通路的抑制（例如ROS的产生）以及靶基因（例如干细胞因子和转化生长因子-α）的表达与舒尼替尼诱导的类似。在异种移植小鸡肿瘤模型中，BJ-1207分别比舒尼替尼或顺铂抑制或相似程度抑制肺肿瘤的生长。总体而言，本研究表明维生素BB-1207在吡啶环的C（6）-位具有氮杂环醇部分的_6-衍生的2,4,5-三甲基吡啶-3-醇化合物抑制NOX活性，并且它是开发抗肺癌药物的有前途的先导化合物。