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 cycloo xygenase (COX) and S-lipoxygenase 5-(LOX), the key enzymes of the arac hidonic acid cascade, and additionally in a cell-free lipid-peroxidati on system. The results were compared with rate constants obtained in p ulse-radiolytic studies. All substances tested showed significant inhi bitory COX and 5-LOX-activity. Marchantin B with two catechol moieties , as in NDGA, exerted an enhanced inhibitory effect in all test system s. The most active compound in the 5-LOX-test was Perrottetin D (IC50 = 0.66 mu M), which was also effective in the COX and lipid-peroxidati on assay. While the rate constant determined by pulse radiolysis was r ather low, EPR studies at elevated temperatures demonstrated for perro tterin D the presence of a pyrogallol-type radical, generated by a fur an-ring opening reaction. In conclusion, all compounds from liverworts investigated possess significant antiinflammatory activities. The res ults let us suggest that all these phenolic compounds can be considere d as promising leads due to their strong radical scavenger potential.