Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues

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• 作者：Guang Liang ; Shulin Yang ; Huiping Zhou ; Lili Shao ; Kexin Huang ; Jian Xiao ; Zhifeng Huang ; Xiaokun Li
• 关键词：Curcumin analogue ; Anti-inflammation ; X-ray diffraction ; Cyclohexanone
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：44
• 期：2
• 页码：915-919
• 全文大小：272 K

文摘

Curcuminoids have been reported to possess multifunctional bioactivities, especially the ability to inhibit proinflammatory induction. Since it has been suggested that the seven-carbon β-diketone linker in curcumin is responsible for its instability, nine mono-carbonyl five-carbon linker containing analogues were designed and synthesized. Their bioactivity against lipopolysaccharide-induced TNF-α amd IL-6 secretion was evaluated by using mouse J774.1 macrophages. The results showed that the 3′-methoxyl plays an important role in bioactivity and cyclohexanone containing analogues exhibited stronger inflammatory inhibition than acetone and cyclopentanone analogues. Subsequently the most active analogue 3c was determined using single-crystal X-ray diffraction. X-ray analysis and comparison with curcumin reveals that the presence of cyclohexanone in 3c, which remotely resembles the 6-membered ring in the enol tautomer in curcumin, may play an important role in the bioactivity. It is suggested that five-carbon linker analogues containing a cyclohexane ring which are synthetically assessable may be pharmacologically important.