Synthesis and activity on free radical processes and inflammation of 9,10-dihydro-5,8-dimethoxy-triptycene-quinones

Three triptycene quinones bearing methoxy groups were prepared following a Diels-Alder methodology and were evaluated for antioxidant and anti-inflammatory activity bearing in mind their structural features that could justify intervention with free radical processes. Improved synthetic pathways were achieved for target molecules 9,10-dihydro-5,8-dimethoxy-9,10-[o]benzenoanthracene-1,4-dione (4), 9,10-dihydro-2-hydroxy-5,8-dimethoxy-9,10-[o]benzenoanthracene-1,4-dione (6), and 9,10-dihydro-2,5,8-trimethoxy-9,10-[o]benzenoanthracene-1,4-dione (9). Under our experimental conditions these compounds showed very significant antioxidant activity offering protection against lipid peroxidation of rat hepatic microsomal fraction while inhibiting the reaction completely at very low concentrations (12.5-80 microM). Moreover, compound 6 that was examined, inhibited by 44% (at 120 microM) lipoxygenase acitvity while the anti-inflammatory activity of the compounds, as assessed by the reduction of the mouse paw edema induced by Freund's complete adjuvant, was significant and comparable to that of indomethacin.