Synthesis and anti-inflammatory evaluation of novel mono-carbonyl analogues of curcumin in LPS-stimulated RAW 264.7 macrophages

Curcumin is a multifunctional natural product with regulatory effects on inflammation. However, a major limitation for the application of curcumin is its poor bioavailability. We previously demonstrated that the mono-carbonyl analogues of curcumin possessed improved pharmacokinetic profiles. In this study, 33 novel mono-carbonyl analogues of curcumin were synthesized and their inhibition against TNF-α and IL-6 release was evaluated in LPS-stimulated RAW 264.7 macrophages. Based on the screening data, quantitative structure–activity relationship was conducted, indicating that electron-withdrawing groups in benzene ring are favourable to anti-inflammatory activities of B-class compounds. Furthermore, compounds AN1 and B82 demonstrated anti-inflammatory abilities in a dose-dependent manner. These raise the possibility that these compounds might serve as potential agents for the treatment of inflammatory diseases.

Graphical abstractCurcumin analogues were synthesized and evaluated for inhibition of LPS-induced TNF-α and IL-6 production in macrophages. The quantitative SAR indicates that electron-withdrawing groups benefit anti-inflammatory activities of B-class compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide