V. I. Lodyato et al. / Bioorg. Med. Chem. Lett. 13 (2003) 1179–1182
Table 1. Inhibiting effects of compounds 3–7 on conjugated diene products formation
1181
Dose kGy
[AO] mMa
Inhibition of CDP formation, %b
3
4
5
6
7
a-T
0.9
1.1
0.4
0.1
85.7ꢃ6.4
86.0ꢃ3.4
67.0ꢃ5.0
26.7ꢃ7.9
48.7ꢃ9.7
53.3ꢃ7.5
68.1ꢃ4.8
46.7ꢃ9.1
63.7ꢃ7.0
60.0ꢃ6.9
63.7ꢃ6.4
27.8ꢃ7.1
aThe phosphatidyl choline concentration was 20 mM.
bPer cent inhibition with respect to a blank experiment, without antioxidant. The confidence interval was calculated for n=3, P=0.95 using the
Student’s t-distribution.
Table 2. Inhibiting effects of compounds 3–7 on TBARS formation
Dose kGy
[AO] mMa
Inhibition of TBARS formation, %b
3
4
5
6
7
a-T
0.9
1.1
0.4
0.1
92.9ꢃ1.9
83.1ꢃ3.8
80.7ꢃ2.9
58.8ꢃ6.3
65.5ꢃ4.4
73.7ꢃ4.2
81.0ꢃ3.3
72.3ꢃ4.7
71.5ꢃ4.3
69.5ꢃ7.3
78.7ꢃ4.1
66.5ꢃ6.6
aThe phosphatidyl choline concentration was 20 mM.
bPer cent inhibition with respect to a blank experiment, without antioxidant. The confidence interval was calculated for n=3, P=0.95 using the
Student’s t-distribution.
References and Notes
Table 3. Hydrophobicity of the compounds 3–7
Compd
k0a
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3
4
5
6
7
0.38
6.39
7.13
12.60
25.20
aHPLC was conducted with Restek Ultra Aqueous C18 column; the
mobile phase consisted of MeOH/H2O (85/15).
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oxidants. Marcel Dekker: New York, 1997.
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terminal part of the side chain. The oriented arrange-
ment of molecules leads to an increase in local concen-
tration of the antioxidant at a definite distance from the
phase interface. The ‘anti-radical shield’ thus formed
protects the membrane from attacks with radical species
coming from the aqueous phase more effectively than
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Because of high efficacy of the antioxidant 3, we intend
to prepare its analogues with various terminal ionogenic
groups. The following study will also include prepara-
tion of a series of compound 3 homologues, and eluci-
dation of the role of alkyl spacer in manifestation of
antioxidant activity.
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Thus, synthesis and inhibiting properties are described
in this paper of a new antioxidant 3 and its analogues
having a non-amphiphilic structure. The importance of
the forming of an amphiphilic domain within the phe-
nolic antioxidant molecule is shown for enhancement of
the efficacy in suppressing the LPO processes, possibly
due to a localization of the radical-inhibiting moieties
within the membrane.
10. Maslovskaya, L. A.; Petrikevich, D. K.; Timoshchuk,
V. A.; Shadyro, O. I. Zh. Obshch. Khim. 1996, 66, 1893 (in
Russian).
11. Maslovskaya, L. A.; Petrikevich, D. K.; Timoshchuk,
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Nauk, Ser. Khim. 1995, 1789 (in Russian).
13. 3: 1H NMR (200 MHz, CDCl3) d 11.91 (s, 1H), 8.52
(br, 1H), 7.42 (br, 1H), 7.22 (s, 1H), 6.78 (s, 1H), 2.40
(m, 4H), 1.74 (m, 4H), 1.44 (s, 9H), 1.26 (m, 21H), MS
m/z 433.40 (M+), 221.25 (MꢂC12H20O3)+, mp 143 ꢁC. 4:
1H NMR (200 MHz, CDCl3) d 8.52 (br, 1H), 7.42 (br,
1H), 7.22 (s, 1H), 6.78 (s, 1H), 3.30 (m, 5H), 2.30 (t,
Acknowledgements
The work was supported, in part, by ISTC Grant
B-434.