Design and synthesis of butyrolactone V derivatives and its anti-inflammatory activity analysis

To design and synthesize an amount of butyrolactone V derivatives, evaluate the anti-inflammatory effects of all the derivatives, look for potential drugs that inhibit inflammatory bowel disease (IBD), and determine the structure-activity relationship (SAR).

The butyrolactone V derivatives were synthesized with high yield by oxidation reaction, substitution reaction, and esterification reaction in sequence, and the production of nitric oxide was assessed in RAW264.7 cells treated with the lipopolysaccharide and the compounds. Then, the target compounds were studied for their activity in dextran sodium sulfate (DSS)-induced ulcerative colitis.

A total of three series of compounds encompassing 60 derivatives of the natural product butyrolactone V were designed and synthesized. The results showed that compounds 5p and 7e could alleviate the symptoms of DSS-induced colitis in mice, including alleviating diarrhea, inhibiting the reduction of colon length, and reducing tissue damage. The preliminary mechanism exploration indicated that compounds 5p and 7e could improve the symptoms of IBD in mice mainly by reducing the expression of chemokines and exerting anti-inflammatory effects.

This study reports the synthesis and the derivatization of butyrolactone V and analysis on anti-inflammatory activity. The most effective compounds 5p and 7e have the potential to be further developed as drugs to treat IBD.