Synthesis and structure–activity relationships of guaiane-type sesquiterpene lactone derivatives with respect to inhibiting NO production in lipopolysaccharide-induced RAW 264.7 macrophages

• Derivatives of guaiane-type sesquiterpene lactone 5 were synthesized.
• Compounds 6g, 7h, 7k, 7i and 8g exhibited significant inhibitory effects on NO production.
• The structure–activity relationships of compounds have been discussed.

A guaiane framework was scaffolded by photochemical rearrangement reactions using α-santonin 1 as a starting material. Then, using a series of reactions, we synthesized the guaiane-type sesquiterpene lactone 5 in high yield. The inhibitory activities of compound 5 and of a series of derivatives on nitric oxide (NO) release were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Compounds 6g, 7h, 7i, 7k and 8g, exhibited significant inhibitory effects on NO production, with IC50 values of 14.8, 22.3, 18.3, 17.4 and 7.0 μM, respectively. Their cytotoxicities were also estimated using an MTT assay. The structure–activity relationships of these compounds were also discussed.

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