Design, synthesis and bioactivity evaluation of fisetin derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury

Acute lung injury (ALI) refers to a common and life-threatening disease attributed to inflammation. However, effective drug treatments have been rare for ALI. Natural products have been considered as a vital source of drug discovery which indicates that it's a workable method to find new anti-inflammatory drugs in natural products. Inspired by the various biological activities of fisetin, we reported the design and synthesis of a series of fisetin derivatives which were also evaluated for their anti-inflammatory activities in J774A.1 macrophages. Most of the obtain derivatives could effectively inhibit the release of IL-6 and TNF-alpha in vitro experiments without cytotoxicity. The most promising compound 5b exhibited significant in vivo anti-inflammatory activity in the model of LPS-induced ALI in mice. On the whole, this study could provide novel candidates for the treatment of ALI.

Automated summary

This study successfully synthesized a series of fisetin derivatives which showed promising anti-inflammatory activities, with compound 5b demonstrating significant in vivo efficacy in a mouse model of LPS-induced ALI. These findings suggest that natural products could be a valuable source for the discovery of new drugs for ALI treatment.