Isoflavone derivatives inhibit NF-κB-dependent transcriptional activity.
The transcription factor NF-κB regulates diverse biological activities, such as inflammatory responses, cell proliferation, and cell survival. Isoflavones are known to have anti-inflammatory and anti-tumor activities, due, in part, to inhibition of NF-κB activity. However, the structural moiety of isoflavones responsible for the inhibition of NF-κB is not clearly understood. In this work, structure-activity relationships of isoflavone derivatives were examined with regard to NF-κB inhibition, using CoMFA and CoMSIA. The results show that substituents at the C-7 and C-4' positions are crucial for the inhibition of TNFα-induced transcriptional activity of NF-κB.
Lee
Sunhee
S
Division of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
Lim
Kyung Chan
KC
Shin
Soon Young
SY
Lee
Young Han
YH
D002460:Cell Line; D018360:Crystallography, X-Ray; D015195:Drug Design; D007529:Isoflavones / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D021281:Quantitative Structure-Activity Relationship; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D007529:Isoflavones; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha