Effect of marchantins and related compounds on 5-lipoxygenase and cyclooxygenase and their antioxidant properties: a structure activity relationship study.

Marchantins and related compounds, isolated from different species of liverworts, were investigated for their inhibitory potential on cyclooxygenase (COX) and 5-lipoxygenase 5-(LOX), the key enzymes of the arachidonic acid cascade, and additionally in a cell-free lipid-peroxidation system. The results were compared with rate constants obtained in pulse-radiolytic studies. All substances tested showed significant inhibitory COX and 5-LOX-activity. Marchantin B with two catechol moieties, as in NDGA, exerted an enhanced inhibitory effect in all test systems. The most active compound in the 5-LOX-test was Perrottetin D (IC(50) = 0.66 μM), which was also effective in the COX and lipid-peroxidation assay. While the rate constant determined by pulse radiolysis was rather low, EPR studies at elevated temperatures demonstrated for perrottetin D the presence of a pyrogallol-type radical, generated by a furan-ring opening reaction. In conclusion, all compounds from liverworts investigated possess significant antiinflammatory activities. The results let us suggest that all these phenolic compounds can be considered as promising leads due to their strong radical scavenger potential.