Interaction of the di-catechols rooperol and nordihydroguaiaretic acid with oxidative systems in the human blood. A structure-activity relationship.

The effects of the di-catechols rooperol [(E)-1,5-bis(3',4'- dihydroxyphenyl)pent-4-en-1-yne; P2] and nordihydroguaiaretic acid (NDGA) on oxidative systems in the human blood were investigated. P2 and NDGA gave comparable results in the inhibition of leukotriene synthesis in the polymorphonuclear leukocyte and prostaglandin synthesis in platelet microsomes. The oxidation states of myeloperoxidase in the presence of H2O2 were also similarly affected by both P2 and NDGA. In these systems, the 4'4'-beta-D-diglucopyranoside of rooperol, hypoxoside [(E)-1,5-bis(4' beta-D-glucopyranosyloxy-3'- hydroxyphenyl) pent-4-en-1-yne; P2A] had no effect. The only system which showed significant differences in the effects of the catechols was the red blood cell. NDGA in the presence of H2O2 had a pronounced haemolytic effect, which did not correlate with its ability to induce methaemoglobin formation, while P2 had a much lower haemolytic effect, but stimulated the oxidation of haemoglobin to a greater extent than NDGA. NDGA is more hydrophobic than P2 which would result in a greater membrane effect. The pent-4-en-1-yne chain which links the catechol moieties in P2 can take part in the resonance structures of the semiquinone free radical, thus assisting in its stabilization and leading to increased methaemoglobin formation. This stabilization is also demonstrated by the fact that P2A affected the oxidation of haemoglobin to nearly the same extent as NDGA.