Natural and newly synthesized hydroxy-1-aryl-isochromans: A class of potential antioxidants and radical scavengers

We investigated the antioxidant and radical scavenging activity of polyphenolic isochromans. To assess the relation between structure and scavenging properties the natural occurring 1-(3′-methoxy-4′-hydroxy)phenyl-6,7-dihydroxy-isochroman (ISO-3, three OH groups) was compared with three newly synthesized derivatives that differ in their degree of hydroxylation by substitution with methoxy-groups (ISO-4: four OH groups; ISO-2: two OH groups and ISO-0: fully methoxylated). We found that ISO-4 is a 2-fold better scavenger for the artificial radical 1,1-diphenyl-2-picrylhydrazyl (DPPH, 100 μM) with an EC50=10.3 μM compared to the natural ISO-3 (EC50=22.4 μM) and to ISO-2 (EC50=25.1 μM), while ISO-0 did not react with DPPH. The scavenging capacity for superoxide enzymatically generated in a hypoxanthin-xanthinoxidase reaction was the highest for ISO-4 (EC50=34.3 μM) compared to those of ISO-3 (EC50=84.0 μM) and ISO-2 (EC50=91.8 μM), while ISO-0 was inactive. In analogy, ISO-4 scavenged peroxynitrite (ONOO−, EC...