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 microM) with an EC50=10.3 microM compared to the natural ISO-3 (EC50=22.4 microM) and to ISO-2 (EC50=25.1 microM), 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 microM) compared to those of ISO-3 (EC50=84.0 microM) and ISO-2 (EC50=91.8 microM), while ISO-0 was inactive. In analogy, ISO-4 scavenged peroxynitrite (ONOO-, EC25=23.0 microM) more effective than ISO-3, ISO-2 and ISO-0. When C6 rat glioma cells loaded with the reactive oxygen/nitrogen (ROS/RNS)-sensitive fluorochrome 2,7-dichlorodihydrofluorescein, were exposed to hydrogen peroxide, the lowest stress level as indicated by the fluorescence signal was detected when the cells were pretreated with ISO-4 or ISO-2 but to a much lesser extent with ISO-3, while ISO-0 did not show any effect. All tested hydroxyisochromans superceded the scavenging effect of trolox.The excellent radical and ROS/RNS scavenging features of the hydroxy-1-aryl isochromans and their simple synthesis let these compounds appear to be interesting candidates for pharmaceutical interventions that protect against the deleterious action of ROS/RNS.
Lorenz
Peter
P
Institute for Medical Neurobiology, Otto-von-Guericke University, Leipziger Strasse 44, D-39120, Magdeburg, Germany.
Zeh
Michael
M
Martens-Lobenhoffer
Jens
J
Schmidt
Harry
H
Wolf
Gerald
G
Horn
Thomas F W
TF
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D005609:Free Radicals