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

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.

Graphical abstractIn this paper, we have synthesized six curcumin analogues without the instable β-diketone moiety. Their bioactivity against LPS-induced TNF-α amd IL-6 secretion was evaluated and crystal structure of the most active compound here was compared with curcumin, which revealed that the structure of cyclohexanone, similar to 6-membered ring formed by hydrogen bond in curcumin, may play an important role in the bioactivity.Figure optionsDownload full-size imageDownload as PowerPoint slide