1158188-88-5Relevant articles and documents
Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors
Jin, Rong,Chen, Qiuxiang,Yao, Song,Bai, Encheng,Fu, Weitao,Wang, Ledan,Wang, Jiabing,Du, Xiaojing,Wei, Tao,Xu, Haineng,Jiang, Chengxi,Qiu, Peihong,Wu, Jianzhang,Li, Wulan,Liang, Guang
, p. 218 - 228 (2018/01/26)
EF24 is an IKKβ inhibitor (IC50: 72 μM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKβ were designed and synthesized. Several IKKβ inhibitors with better activities than EF24 were screened out and B3 showed best IKKβ inhibitory (IC50: 6.6 μM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKβ phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKKβ-NF-κB signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKKβ inhibitor as anti-tumor precursor.
Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors
Hosoya, Takahiro,Nakata, Asami,Yamasaki, Fumie,Abas, Faridah,Shaari, Khozirah,Lajis, Nordin Hj,Morita, Hiroshi
experimental part, p. 166 - 176 (2012/05/20)
Anti-melanogenesis screening of 47 synthesized curcumin-like diarylpentanoid analogues was performed to show that some had a potent inhibitory effect on the melanogenesis in B16 melanoma cells. Their actions were considered to be mostly due to tyrosinase inhibition, tyrosinase expression inhibition, and melanin pigment degradation. The structure-activity relationships of those curcumin-like diarylpentanoid analogues which inhibited the melanogenesis and tyrosinase activity were also discussed. Of those compounds assayed, (2E,6E)-2,6-bis(2,5- dimethoxybenzylidene)cyclohexanone showed the most potent anti-melanogenesis effect, the mechanism of which is considered to be the degradation of the melanin pigment in B16 melanoma cells, affecting neither the tyrosinase activity nor tyrosinase expression. The Japanese Society of Pharmacognosy and Springer 2011.
Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents
Liang, Guang,Shao, Lili,Wang, Yi,Zhao, Chengguang,Chu, Yanhui,Xiao, Jian,Zhao, Yu,Li, Xiaokun,Yang, Shulin
experimental part, p. 2623 - 2631 (2009/09/06)
Curcumin has a surprisingly wide range of chemo-preventive and chemo-therapeutic activities and is under investigation for the treatment of various human cancers. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Although a number of synthetic modifications of curcumin have been studied intensively in order to develop a molecule with enhanced bioactivities, few synthetic studies were done for the improvement of pharmacokinetic profiles. In the present study, a series of mono-carbonyl analogues of curcumin were designed and synthesized by deleting the reactive β-diketone moiety, which was considered to be responsible for the pharmacokinetic limitation of curcumin. The results of the in vitro stability studies and in vivo pharmacokinetic studies indicated that the stability of these mono-carbonyl analogues was greatly enhanced in vitro and their pharmacokinetic profiles were also significantly improved in vivo. Furthermore, the cytotoxic activities of mono-carbonyl analogues were evaluated in seven different tumor cell lines by MTT assay and the structure-activity relation (SAR) was discussed and concluded. The results suggest that the five-carbon linker-containing analogues of curcumin may be favorable for the curcumin-based drug development both pharmacokinetically and pharmacologically.
