2602
Y.-S. Jung et al. / Bioorg. Med. Chem. Lett. 12 (2002) 2599–2602
In conclusion, we have synthesized 4-hydroxy-
phenylacetic acid amides and 4-hydroxycinnamamides,
and evaluated their antioxidant activities. Compounds
exhibiting potent inhibition of lipid peroxidation as well
as DPPH radical scavenging activity were selected, and
their structure–activity relationships were discussed.
Furthermore, we examined the ability to protect neu-
rons from various oxidative stresses in primary cultured
rat cortical cells. We found that 6f is the most potent
and promising antioxidant exerting prominent neuro-
protective action. Based on these results, 6f may provide
a useful therapeutic potential for the treatment of neu-
rodegenerative disorders caused by oxidative stress.
6. Chabrier, P.-E.; Auguet, M.; Spinnewyn, B.; Auvin, S.;
Cornet, S.; Demerle-Pallardy, C.; Guilmard-Favre, C.; Marin,
J.-G.; Pignol, B.; Gillard-Roubert, V.; Roussillot-Charnet, C.;
Schulz, J.; Viossat, I.; Bigg, D.; Moncada, S. Proc. Natl. Acad.
Sci. U.S.A. 1999, 96, 10824.
7. Park, N.-S.; Ha, D.-C.; Kim, H.-S.; Choi, J.-K. Kor. J.
Med. Chem. 1991, 1, 2.
8. Jung, Y.-S.; Kang, T.-S.; Lee, J.-C.; Seong, C.-M.; Ham,
W.-H.; Park, N.-S. Synth. Commun. 2001, 31, 455.
9. TBARS: Brain tissue from male Sprague–Dawley rats
(about 10-weeks old) was obtained after decapitation and
homogenated in ice-cold 10 mM Tris–HCl buffer (pH. 7.4)
using a Teflon-glass homogenizer. The homogenate was cen-
trifuged for 10 min at 1000 Â g, and the supernatant was used
in the test. Lipid peroxidation was stimulated in assays con-
taining 250 mL rat brain homogenate by additions of 0.02 mM
FeCl2 and 0.25 mM ascorbic acid, and the mixture was incu-
bated for 30 min at 37 ꢀC. The reaction was stopped by the
addition of 0.05 mL of 35% perchloric acid. After centrifuga-
tion for 10 min at 1000 Â g, 200 mL of the resulting super-
natant was added to 100 mL of an aqueous solution containing
0.5% TBA and reacted at 80 ꢀC for 1 h. Then, the reaction
mixture was cooled to room temperature, and its absorbance
at 532 nm was measured. Typical TBARS formation in brain
homogenate was calculated from the absorbance at 532 nm
using 1,1,3,3-tetraethoxypropane as an external standard.
10. Stocks, J.; Gutteridge, J. M. C.; Sharp, R. J.; Dormandy,
T. L. Clin. Sci. Mol. Med. 1974, 47, 215.
Acknowledgements
This work was supported by grants from Korea Science
& Engineering Foundation (R01–2001–00160), from
Plant Diversity Research Center of 21st Century Fron-
tier Research Program (PF002103–04), and from the
Ministry of Science and Technology in Korea.
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