Synthesis and in vitro evaluation of homoisoflavonoids as potent inhibitors of nitric oxide production in RAW-264.7 cells

Syntheses of natural homoisoflavonoids, (±)-portulacanones A-C (4, 8 and 9), portulacanone D (6), isolated from Portulaca oleracea L. (POL) and their derivatives (3, 5 and 7) have been achieved for the first time along with the synthesis of known derivatives (1 and 2) and their in vitro inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages was evaluated as an indicator of anti-inflammatory activity. All the compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without obvious cytotoxicity. Compounds 3 (97.2% at 10 μM; IC₅₀ = 1.26 µM) followed by 6 (portulacanone D) (92.5% at 10 μM; IC₅₀ = 2.09 µM), 1 (91.4% at 10 μM; IC₅₀ = 1.75 µM) and 7 (83.0% at 10 μM; IC₅₀ = 2.91 µM) were the most potent from the series. This finding was further correlated with the suppressed expression of iNOS induced by LPS. Our promising preliminary results may provide the basis for the assessment of compound 3 as a lead structure for a NO production-targeted anti-inflammatory drug development and also could support the usefulness of POL as a folklore medicinal plant in the treatment of inflammatory diseases.

Anti-inflammatory; Homoisoflavonoids; Nitric oxide; Portulacanones; RAW-264.7 macrophages.