Nuclear factor-κB ( NF-κB ) 為重要的轉錄因子，當細胞受到外來刺激時，NF-κB 將會活化造成細胞異常增生與細胞抗凋亡現象而導致病變。2002年由 Medical Molecular Design 公司發表的 IMD-0354 為有效的 NF-κB 抑制劑，本研究以 IMD-0354 為前導化合物，合成三種系列的衍生物，探討與前導化合物的結構與活性關係。第一系列以 DCC 偶合反應合成苯甲醯苯胺衍生物，第二系列以霍鈉-沃茲沃斯-艾蒙斯反應合成二苯乙烯衍生物，第三系列以 DCC 偶合反應合成 N-substituted indole 衍生物，並測試其對於 NF-κB 的抑制活性。生物活性結果顯示衍生物受到三氟甲基官能基、醯胺鍵結上氫鍵作用力與衍生物整體剛性的影響。N-substituted indole 衍生物對於 NF-κB 的抑制活性不及苯甲醯苯胺與二苯乙烯衍生物。50 μM 濃度下以 WY4102 與 WY4201 對於 NF-κB 有最佳的抑制活性。 Nuclear factor-κB ( NF-κB ) is an important transcription factor. The cell is stimulated by stress, cytokines and toxic metals, leading to NF-κB activation and overexpress of NF-κB would result in prolification of cell or development of tumor. We took a novel potential NF-κB inhibitor: IMD-0354 as lead compound, and designed, synthesized three series of derivatives. The benzamide analogs were synthesized by SN2 reaction and DCC coupling reaction. The stilbene derivatives were synthesized by Horner - Wadsworth - Emmons reaction, and N-substituted indole derivatives are synthesized by DCC coupling reaction. The structure-activity relationship shows that the trifluoromethyl group, hydrogen bond effect on amide and degree of rigidity of compounds will affect the inhibition of NF-κB.
