Synthesis of Water-soluble IMD-0354 Derivatives and Evaluating Their IKKβ Inhibition

• Main Authors: Wu, Han-Wei, 吳翰維
• Other Authors: Wu, Yu-Shan
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/43227561410254100674

碩士 === 東海大學 === 化學系 === 102 === NF-κB is a transcription factor that controls the expression of genome involved in immune responses, apoptosis and cell cycle. In cytoplasm, NF-κB is inhibitid by IκB, but would be activated upon phosphorylation by IKKβ. In previous study, IMD-0354 and its derivatives showed good inhibition of IKKβ, but unfortunately exhibit poor water-solubility. In this thesis, we have a series of synthesized new IMD-0354 derivatives using more water soluble substituted pyridine as core structures. The derivatives WY8116 and WY8118 were found to be good IKKβ inhibitors with IC50 values of 0.78 and 2.52±0.43μM. Docking studies of IKKβ structure with the derivatives revealed an important interaction between pyrindine ring and Tyr98 in active site. These derivatives have good potential in developing into new anti-inflammatory drugs.