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Additionally, the analogues of the hanultarin were also prepared to
determine the structural effect on the cell toxicity. The cytotoxicity
experiments revealed that the diester derivatives were more active
than the mono ester derivatives against various cancer cell lines.
The IC50 values of the ( )-1,4-O-diferuloyl-secoisolariciresinol were
in the range of the several
l molar concentration, which is remark-
able in that simple covalent bonds between the ferulic acid and
secoisolariciresinol cause a cytotoxic effect. The immunocyto-
chemical analysis of the A549 cells after treatment of the mono
or diester derivatives showed the cell shrinkages, which might be
originated from the inhibitory effect of the polymerization of actin
or microtubule fibers.
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Now further modification of the hanultarin derivative and a
detailed mechanistic analysis of the cytotoxicity are in progress.
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8606.
19. See the Supplementary data for the detailed experimental.
20. Full characterization data:
Acknowledgments
( )-hanultarin (11a): IR
mmax: 3419, 2917, 2850, 1697, 1602, 1515, 1269, 1156
cmꢀ1 1H NMR (400 MHz, CD3OD) d 1.92 (1H, m), 2.19 (1H, m), 2.56 (2H, d,
:
This research was partly supported by the Basic Science
Research Program through the National Research Foundation of
Korea (NRF) funded by the Ministry of Education, Science and
Technology (2009-0071513).
J = 7.6 Hz), 2.65 (2H, dd J = 7.2, 13.6 Hz), 3.49 (1H, dd, J = 6.0, 14.4 Hz), 3.62 (1H,
dd, J = ), 3.66 (3H, s), 3.67 (3H, s), 3.82 (3H, s), 4.04 (1H, dd, J = 6.4, 11.2 Hz),
4.28 (1H, dd, J = 6.0, 11.2 Hz), 6.30 (1H, d, J = 16 Hz), 6.51 (3H, m), 6.57 (1H, d,
J = 2 Hz), 6.62 (2H, dd, J = 2, 8 Hz), 6.75 (1H, d, J = 8 Hz), 7.00 (1H, dd, J = 1.6,
8.0 Hz), 7.11 (1H, d, J = 2.0 Hz), 7.51 (1H, d, J = 16.0 Hz). 13C NMR (100 MHz,
CD3OD) 35.53, 36.01, 40.78, 56.33, 56.61, 62.87, 66.13, 111.80, 113.40, 113.53,
115.70, 116.00, 116.05, 116.63, 122.81, 122.85, 127.83, 133.39, 133.87, 145.70,
145.79, 147.00, 148.99, 149.02, 149.54, 150.80, 169.45; ESI-MS: Calcd
Supplementary data
538.2203. Found: 537.2130 [MꢀH]; observed ½a D20
ꢁ
ꢀ0.15 (c 0.1, MeOH).
Supplementary data associated with this article can be found, in
( )-1,4-O-di-feruloyl-secoisolariciresionol (11b): IR mmax
:
3418, 2926, 1698,
1514, 1267, 1157 cmꢀ1 1H NMR (400 MHz, CDCl3) d 2.21 (2H, m), 2.72 (4H,
;
m), 3.77 (6H, s), 3.91 (6H, s), 4.21 (2H, dd, J = 5.2, 11.2 Hz), 4.39 (2H, dd, J = 5.6,
11.2 Hz), 5.89 (2H, s), 6.28 (2H, d, J = 16.0 Hz), 6.52 (2H, d, J = 2.0 Hz), 6.61 (2H,
dd, J = 2.4, 8.0 Hz), 6.80 (2H, d, J = 8.0 Hz), 6.90 (2H, d, J = 8.0 Hz), 7.01 (2H, d,
J = 2.0 Hz), 7.06 (2H, dd, J = 1.6, 8.0 Hz), 7.58 (2H, d, J = 16.0 Hz); 13C NMR
(100 MHz, CDCl3) d 35.26, 40.12, 55.74, 55.96, 64.44, 109.44, 111.24, 114.11,
114.71, 115.18, 121.71, 123.07, 126.82, 131.69, 143.90, 145.13, 146.43, 146.76,
148.05, 167.23; ESI-MS: Calcd 714.2676. Found: 713.2604 [MꢀH]; observed
References and notes
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½ ꢁ ꢀ0.01 (c 0.1, MeOH).
a 2D0
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