Antioxidant activity of pinoline analogues in the LDL oxidation model

Recently it has been shown that pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) is as potent as melatonin in the inhibition of lipid peroxidation. We have synthesized some 1-aryl-1,2,3,4-tetrahydro-beta-carbolines and investigated their ability to prevent LDL copper-induced peroxidation in comparison with melatonin and pinoline. In this model, we found that the introduction of a phenyl group in position 1 of the beta-carboline skeleton resulted in more active compounds. The presence of a methoxy group in position 6 of the beta-carboline skeleton had a beneficial influence on this activity, whereas replacement of this methoxy by an ethyl side chain increased the antioxidant potency. On the other hand, substitution of the 1-phenyl substituent with a methoxy group did not affect the activity.Finally, compounds bearing a propyl group on position 2 of the beta-carboline skeleton are the most active. Taken together these results confirm the role of lipophilicity in the ability to inhibit LDL oxidation.