myrigalone-b and 1-1-diphenyl-2-picrylhydrazyl

A naturally occurring flavonoid, myrigalone B (2',6' -dihydroxy-4'-methoxy-3',5'-dimethyl-dihydrochal-cone) is an effective antioxidant and scavenger of the diphenylpicrylhydrazyl radical, while the closely related angoletin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethyl-dihydrochalcone) is inactive. From NMR spectra, it appears that myrigalone B has a time-averaged conformation in which the substituted aromatic ring is orthogonal to the carbonyl group, while angoletin is coplanar. By donating a phenolic hydrogen in radical scavenging, myrigalone B will lose its symmetrical structure and may thereby change to a coplanar conformation forming a strong intramolecular hydrogen bond between the remaining phenolic hydrogen and the carbonyl group. The energy gain entailed would then appear to be a driving force for the radical scavenging by myrigalone B. Angoletin, being coplanar, lacks this driving force. To verify this hypothesis, the conformation and radical scavenging activity of a series of phenolic acetophenones were studied. All substances that had an orthogonal conformation and could form intramolecular hydrogen bonds by loss of a phenolic hydrogen were DPPH scavengers, while compounds lacking these properties were inactive. From this, we propose that formation of intramolecular hydrogen bonds may lead to radical scavenging activity.

Topics: Acetophenones; Animals; Antioxidants; Bepridil; Biphenyl Compounds; Chalcone; Chalcones; Flavonoids; Free Radical Scavengers; Free Radicals; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Picrates; Plants; Protons; Rats; Structure-Activity Relationship

Antioxidant and radical scavenging effects were studied of a diethyl ether extract of the fruit exudate of Myrica gale L., and of C-methylated dihydrochalcones isolated from it. Isolated hepatocytes and liver mitochondria from the rat were incubated with tertbutyl hydroperoxide, and lipid peroxidation measured by the yield of thiobarbituric acid reactive substances. The main antioxidant of the extract, myrigalone B (MyB), inhibited lipid peroxidation in hepatocytes with an IC50 value of 23 +/- 1 microM, whereas in mitochondria the value was 5.2 +/- 0.1 microM. The fruit extract itself inhibited peroxidation in hepatocytes with an IC50 value of 7.0 +/- 0.2 microM calculated according to its MyB content, and in mitochondria with an IC50 of 1.7 +/- 0.1 microM. Other myrigalones were considerably less active or inactive as antioxidants. The IC50 of promethazine, an established inhibitor of lipid peroxidation, was 3.8 +/- 0.4 microM in mitochondria./ Both MyB and the fruit extract caused scavenging of the diphenylpicrylhydrazyl (DPPH) radical with IC50 values of 32 +/- 1 microM and 14 +/- 1 microM (as MyB), respectively. Peroxidation in linoleic acid catalyzed by soybean 15-lipoxygenase was inhibited by MyB (IC50 = 23 +/- 1 microM calculated as MyB; corresponding to an extract concentration of 71 +/- 3 microgram(s)/ml). However, the extract content of myrigalone A, itself a fairly potent inhibitor of 15-lipoxygenase, may contribute significantly to the latter effect.

Topics: Animals; Antioxidants; Bepridil; Biphenyl Compounds; Cells, Cultured; Chalcone; Chalcones; Flavonoids; Free Radical Scavengers; Lipid Peroxidation; Lipoxygenase Inhibitors; Liver; Male; Methylation; Picrates; Plant Extracts; Plants; Rats; Rats, Wistar