轉錄因子 NF-κB (nuclear factor kappaB) 的活化，會引起發炎蛋白及抗細胞凋亡蛋白生成，當其過度表現時可能形成癌細胞。因此當細胞受到外來刺激會引起 NF-κB 的活化，阻止其過度表現成為預防癌症的重要課題。本研究選擇 NF-κB 的抑制劑 ─ IMD-0354 [N-(3,5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide] 作為先導化合物，並參考天然物白藜蘆醇 ( Resveratrol ) 衍生物的結構及取代，合成一系列衍生物，探討其結構與活性之間的關係。研究結果發現在相同取代下，IMD-0354 衍生物抑制 NF-κB 活性的效果較白藜蘆醇衍生物優異，顯示化合物在 NF-κB 的活性部位具氫鍵作用力，且可有效抑制 NF-κB 的活性表現。 Nuclear factor kappa B (NF-κB) is a transcription factor which regulates expression of numerous inflammatory genes and mediates antiapoptotic genes in cell. Highly activated NF-κB level would result in over-expression of these genes and eventually lead to cancer. In this study, NF-κB inhibitors IMD-0354 (N-(3,5-bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide) and natural product resveratrol are selected as lead compounds. A series of IMD-0354 derivatives and Resveratrol are synthesized and their structure-activity relationships are established. NF-κB inhibition experiments show that IMD-0354 derivatives inhibit NF-κB activity stronger than resveratrol derivatives when their substituents are identical. This indicates hydrogen bonds exist between active analogs and NF-κB binding site, and therefore hydrogen bond donors/acceptors are required for NF-κB inhibition.
