To develop a more potent NFκB inhibitor from salicylic acid which is known to inhibit activity of NFκB, a transcription factor regulating genes involved in immunity, inflammation and tumorigenesis, derivatives of salicylic acid (SA) where the 5 position, carboxyl or hydroxyl group was modified were treated in HCT116 cells transfected with an NFκB dependent luciferase gene and LPS-stimulated RAW264.7 cells. Amidation of the carboxylic group or substitution of chlorine at the 5 position increased the ability of SA to suppress the expression of NFκB dependent luciferase and inducible nitric oxide synthase, a product of an NFκB target gene. Moreover, simultaneous amidation and chlorination of SA (5-chlorosalicylamide; 5-CSAM) conferred an additive NFκB inhibitory activity on SA. To further enhance the inhibitory activity, N-modification was imposed on 5-CSAM. N-(5-chlorosalicyloyl)phenethylamine (5-CSPA), N-(5-chlorosalicyloyl)3-phenylpropylamine (5-CSPPA) and N-(5-chlorosalicyloyl)4-hydroxyphenylethylamine (5-CSHPA) showed greater potencies for inhibiting NFκB activity than other derivatives. Their IC₅₀s’ in the luciferase assay measured 15 μM (5-CSPA), 17 μM (5-CSPPA) and 91 μM (5-CSHPA). Rectal administration of 5-CSPA ameliorated TNBS-induced rat colitis, which was more effective than a conventional drug, 5-aminosalicylic acid. These data may provide useful information for development of a therapeutic agent for treatment of diseases where NFκB plays a critical role in the pathogenic progresses.

为了从水杨酸开发更有效的NFκB抑制剂，已知它能抑制NFκB的活性，NFκB是一种调节免疫，炎症和肿瘤发生的转录因子调节基因，是水杨酸（SA）的5位，羧基或羟基被修饰的衍生物在转染了NFκB依赖性荧光素酶基因的HCT116细胞和LPS刺激的RAW264.7细胞中进行了处理。羧基的酰胺化或5位上的氯取代增强了SA抑制NFκB依赖的荧光素酶和可诱导的一氧化氮合酶（NFκB靶基因的产物）表达的能力。此外，SA（5-氯水杨酰胺； 5-CSAM）的同时酰胺化和氯化反应赋予SANFκB加性抑制活性。为了进一步增强抑制活性，对5-CSAM进行N-修饰。N-（5-氯水杨酰基）苯乙胺（5-CSPA），N-（5-氯水杨酰基）3-苯丙胺（5-CSPPA）和N-（5-氯水杨酰基）4-羟基苯乙胺（5-CSHPA）显示出更大的抑制力NFκB的活性高于其他衍生物。他们的IC萤光素酶测定中的₅₀ s'测量为15μM（5-CSPA），17μM（5-CSPPA）和91μM（5-CSHPA）。直肠给药5-CSPA可改善TNBS诱导的大鼠结肠炎，它比常规药物5-氨基水杨酸更有效。这些数据可为开发用于治疗其中NFκB在致病性进程中起关键作用的疾病的治疗剂提供有用的信息。