Synthesis and antioxidant activities of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives

Article abstract of DOI:10.1016/j.bmcl.2012.11.006

A series of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives 4a ₁-4n₂ were designed and synthesized based on the 2-oxo-quinoline structure core as novel antioxidants. In vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidants ascorbic acid, BHT and BHA, employing DPPH assay, ABTS⁺ assay, O₂^- assay and OH assay. The results showed that IC₅₀ of most compounds were lower than standard value 10 mg/mL, indicating good antioxidant activities of these compounds. In addition, in vitro antioxidant activities screening revealed that 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of compounds 4b₂, 4e ₁, 4e₂ and 4g₂, 2,2′-azinobis-(3- ethylbenzthiazoline-6-sulphonate) cation (ABTS⁺) radical scavenging activities of compounds 4a₁, 4e₁, 4e₂, 4f ₁, 4f₂, 4g₁, 4g₂, 4h₁, 4h₂, 4k₁, 4k₂, 4n₁ and 4n ₂, superoxide anion radical scavenging activities of 4b₁, 4e₁, 4f₂, 4j₁, 4k₁, 4k₂, 4m₁, 4m₂, and 4n₂, and hydroxyl radical scavenging activity of almost all the compounds except 4f₁, 4f ₂, 4j₂, 4l₁ and 4l₂ were better than that of the commercial antioxidant butylated hydroxytoluene (BHT).

Full text of DOI:10.1016/j.bmcl.2012.11.006

Bioorganic & Medicinal Chemistry Letters 23 (2013) 107–111
Contents lists available at SciVerse ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Synthesis and antioxidant activities of 2-oxo-quinoline-3-carbaldehyde
Schiff-base derivatives
Ye Zhang a,b,c, , Yilin Fang b,c, , Hong Liang c, Hengshan Wang c, Kun Hu c, Xianxian Liu b, Xianghui Yi b,d,
,
⇑
Yan Peng c,
⇑
a School of Chemistry and Chemical Engineering, South Central University, Hunan 410083, PR China
b Department of Chemistry, Guilin Normal College, Guangxi 541001, PR China
c Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Chemical Engineering, Guangxi Normal University,
Guangxi 541004, PR China
d Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Guilin 541006, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 July 2012
Revised 29 October 2012
Accepted 2 November 2012
Available online 10 November 2012
A series of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives 4a1–4n2 were designed and synthe-
sized based on the 2-oxo-quinoline structure core as novel antioxidants. In vitro antioxidant activities
of these compounds were evaluated and compared with commercial antioxidants ascorbic acid, BHT
ꢀÅ
and BHA, employing DPPHÅ assay, ABTS+Å assay, O2 assay and OHÅ assay. The results showed that IC50
of most compounds were lower than standard value 10 mg/mL, indicating good antioxidant activities
of these compounds. In addition, in vitro antioxidant activities screening revealed that 2,2-diphenyl-1-
picrylhydrazyl (DPPH) radical scavenging activities of compounds 4b2, 4e1, 4e2 and 4g2, 2,20-azinobis-
(3-ethylbenzthiazoline-6-sulphonate) cation (ABTS+) radical scavenging activities of compounds 4a1,
4e1, 4e2, 4f1, 4f2, 4g1, 4g2, 4h1, 4h2, 4k1, 4k2, 4n1 and 4n2, superoxide anion radical scavenging activities
of 4b1, 4e1, 4f2, 4j1, 4k1, 4k2, 4m1, 4m2, and 4n2, and hydroxyl radical scavenging activity of almost all the
compounds except 4f1, 4f2, 4j2, 4l1 and 4l2 were better than that of the commercial antioxidant butylated
hydroxytoluene (BHT).
Keywords:
Antioxidant activity
Radical scavenging activity
2-Oxo-quinoline-3-carbaldehyde
Schiff-base
Ó 2012 Elsevier Ltd. All rights reserved.
The significance of free radicals and reactive oxygen species
(ROS) in the pathogenicity of numerous diseases,1–5 including var-
ious chronic and age-related diseases has attracted considerable
attention. Antioxidants are recently fabricated as the drug candi-
dates to counter these multifarious diseases, such as carcinogene-
sis, inflammation, atherogenesis and aging in aerobic organisms.6,7
Small quantities of dietetic compositions are seriously considered
to confront the ill effects of the free radicals and ROS.
It is known that quinolines and its derivatives exhibit exten-
sively biological and pharmacological activities,8–11 thus consider-
able efforts have been devoted to design and synthesize functional
quinoline derivatives over the past decades. Among the various
existing active skeletons of quinolines, 2-oxo-quinoline is a kind
of alkaloid which exists in nature widely as same as quinoline.
Researchers have long explored natural products in the quest for
new drugs, so those compounds with a 2-oxo-quinoline structure
core (Fig. 1) have been studied and it have been found that they
own preferable biological activities such as anticancer, antiprolifer-
ation and anti-inflammation.12–15 Previous studies have revealed
that various diseases are diagnostically associated with free radi-
cals and ROS.1–5 In addition, the potential therapeutic or preven-
tive effects of antioxidative agents may be included in the course
of inhibition of carcinogenesis and cancer,16–19 it is thus to expect
that 2-oxo-quinoline derivatives may contribute to good antioxi-
dant activity. So 2-oxo-quinoline structure is chosen in the present
work as active pharmacy core and some structural modifications
are designed to explore their antioxidant activities. Schiff-bases
are multifunctional groups and they are able to improve various
biological and pharmacological activities of a pharmacy core, such
as antitumor, antioxidation and antibacterial activities.20 In our
previous work, Schiff-bases groups have been design to improve
the antioxidant activities of 7-benzyloxy-coumarin core.21 There-
fore, well-designed functional groups would enable a fine-tuning
of special properties of a pharmacy core. Our previous studies have
showed that good electronic fluidity may contribute to superior
antioxidant activity,21 so Schiff-bases groups are designed to intro-
duce at position 3 of 2-oxo-quinoline structural core to expect to
increase the donor–acceptor electronic effect, as well as the elec-
tronic fluidity and thus to enhance their antioxidant activities.
Our present work in this paper is to design and synthesize
2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives, and to
evaluate their in vitro antioxidant activities.
⇑
Corresponding authors. Tel.: +86 773 282 3285; fax: +86 773 280 6321.
E-mail address: yixianghui2008@yahoo.com.cn (X. Yi).
Co-first author: these authors contributed equally to this work.
0960-894X/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2012.11.006

108
Y. Zhang et al. / Bioorg. Med. Chem. Lett. 23 (2013) 107–111
butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA)
and ascorbic acid were also measured for comparison. The tested
results were shown in Table 1.
N
H
O
It can be seen from Table 1 that almost all the compounds ex-
cept 4c1–4d1, 4i2, 4j2 and 4l2 showed radical scavenging activities
in DPPHÅ assay. It was important to note that compounds 4b2, 4e1,
4e2 and 4g2 showed better DPPH radical scavenging activity than
the commercial synthetic antioxidant BHT, with IC50 values of
Figure 1. 2-oxo-quinoline.
2-Oxo-quinoline-3-carbaldehyde Schiff-base derivatives 4a1–4n2
were synthesized as outlined in Scheme 1. 2-Chloro-quinoline-
3-carbaldehyde derivatives were obtained through
Vilsmeier-Haack-Arnold reaction, which contained the condensa-
tion of acetanilide derivatives 1 with N,N-dimethylformamide
(DMF) in the presence of phosphorusoxychloride. Compounds 3
were then synthesized in good yields by the hydrolytic reaction
63.24, 22.76, 26.16 and 62.41 lM, respectively. Moreover, com-
2
pounds 4e1 and 4e2 even exhibited stronger DPPH radical scaveng-
ing activities than ascorbic acid. Evidently, of all the compounds,
4e1 exhibited the best radical scavenging activity in this assay.
Compounds 4f1, 4f2 and 4g1 showed effective DPPH radical scav-
enging activities close to that of BHT, with IC50 of 92.10, 88.54
of
2 in the presence of 70% acetic acid aqueous solution.
and 76.50 lM, respectively. Compound 4m2 showed very low
2-Oxo-quinoline-3-carbaldehyde Schiff-base 4a1–4n2 were then
obtained in good yields by the condensation of 3 with different
primarily amines or hydraziniums in hot ethanol, respectively.
The structures of compounds 4a1–4n2 were confirmed by NMR
and mass spectra.22
In vitro antioxidant activities were assayed against 2,2-diphe-
nyl-1-picrylhydrazyl (DPPH),21 2,20-azinobis-(3-ethylbenzthiazo-
line-6-sulphonate) cation (ABTS+),23 hydroxyl24 and superoxide
anion25 radicals, respectively, according to the literatures21,23–25
with a little modification. The values of IC50, the effective concen-
tration at which 50% of the radicals were scavenged, were tested to
evaluate the antioxidant activities. Generally, a lower IC50 value
demonstrated greater antioxidant activity and IC50 values of less
than 10 mg/mL usually indicated potent activities in antioxidant
properties.26 IC50 of three commercial synthetic antioxidants
DPPH radical scavenging activity and its IC50 was determined to
be 1.10 mg/mL and much lower than the standard value 10 mg/
mL,26 indicating good DPPH radical scavenging activities of these
compounds. The DPPHÅ scavenging activities of tested was found
to be in the order of BHA > 4e1 > 4e2 > ascorbic acid > 4g2 > 4b2 >
BHT > 4g1 > 4f2 > 4f1 > 4h2 > 4a1 > 4a2 > 4h1 > 4i1 > 4j1 > 4b1 > 4d2 >
> 4a1 > 4a2 > 4h1 > 4i1 > 4j1 > 4b1 > 4d2 > 4k2 > 4k1 > 4n1 > 4m1
> 4n2 > 4m2. On the basis of the above observation, the electron-
donating groups such as phenol, aniline, hydrazino and amino
groups showed positive influence on DPPHÅ scavenging activities,
while the electron-withdrawing groups such as nitro, carboxylic
and sulfamic groups exhibited negative effect. Besides, methyl in
6 position of quinolone ring, benzyl and aliphatic hydrocarbon sub-
stituents containing in Schiff-bases groups also appeared to have
important influences on the DPPH radical scavenging activity.
R1
R1
CHO
O
R1
R2
R1
CHO
(b)
O
N
(a)
(c)
N
H
N
H
N
H
O
N
Cl
1
2
3
4
1a: R1 = H
2a: R1 = H
3a: R1 = H
1b: R1 = CH3
2b: R1 = CH3
3b: R1 = CH3
Scheme 1. Synthetic route of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives. Reagents and conditions: (a) DMF/POCl3, 90 °C; (b) 70% acetic acid aqueous solution,
95 °C; (c) R2-NH2, ethanol, 80 °C.

Y. Zhang et al. / Bioorg. Med. Chem. Lett. 23 (2013) 107–111
109
Table 1
Radicals scavenging activities of compounds 4
ꢀÅ
Compounds
DPPHÅ IC50
(l
M)
ABTS+Å IC50
(lM)
O2 IC50
(l
M)
OHÅ IC50
(lM)
4a1
4a2
4b1
4b2
4c1
117.67 0.58
159.83 0.72
439.47 0.47
63.24 0.29
None
31.82 0.45
38.87 0.53
1814.17 0.79
43.28 0.61
367.54 0.53
607.36 0.68
1210.01 0.97
1190.79 1.12
11.70 0.12
8.24 0.07
7.15 0.09
5.24 0.15
11.81 0.21
8.47 0.18
11.36 0.31
8.25 0.11
142.03 0.67
143.88 0.55
1609.77 1.14 (0.53 0.09)a
1202.06 1.34
20.57 0.25
11.27 0.16
438.07 0.77
222.1 0.82
485.07 0.91
881.85 0.76
8.91 0.16
462.66 0.88
389.43 0.65
245.96 0.92
378.87 0.97
328.96 0.85
310.04 0.65
467.02 0.56
1481.85 1.45 (0.34 0.05)a
237.17 0.75
286.12 0.84
306.38 0.65
235.07 0.55
305.80 0. 91
309.29 0.83
None
2013.57 1.14
1983.15 1.65
7678.28 2.25
3564.59 1.42
3137.21 1.31
6918.84 1.75
3314.35 1.36
4183.60 1.49
1659.90 1.17
1346.70 1.45
None
4c2
None
None
4d1
4d2
4e1
4e2
4f1
4f2
4g1
4g2
4h1
4h2
4i1
4i2
4j1
497.61 0.85
22.76 0.18
26.16 0.15
92.1 0.37
88.54 0.51
76.50 0.49
62.41 0.23
170.14 0.43
108.97 0.55
190.24 0.64
None
265.53 0.67
None
729.32 0.44
641.02 0.78
1662.8 1.32
None
2847.26 1.18
3580.86 1.94 (1.10 0.07)a
1285.54 1.48
3347.31 0.96
65.85 0.50
43.81 0.65
20.25 0.25
None
1002.81 1.25
1468.98 1.17
244.87 0.88
350.22 0.75
375.07 0.62
748.61 0.85
265.53 0.57
None
None
None
None
169.14 0.78
257.86 0.64
183.56 0.55
153.28 0.73
381.47 0.86
408.70 0.95
197.33 0.72
209.10 0.55
255.68 0.53
146.51 0.63
253.66 0.66
15.56 0.22
38.83 0.57
4j2
4k1
4k2
4l1
365.24 0.69
789.55 0.84
None
4l2
None
4m1
4m2
4n1
4n2
BHT
Ascorbic acid
BHA
5089.19 1.98
4688.16 1.75
8725.12 2.05 (2.15 0.25)a
5827.03 1.85
9.17 0.15
36.98 0.35
12.83 0.29
1.02 0.05
24676.47 1.76
73.81 0.49
26792.57 1.58
None: ineffective.
a
IC50 of the lowest radical scavenging activities compounds countered by mg/mL unit.
ABTS+ radical assay is a classic and good model for estimating
the antioxidant activities of hydrogen-donating and chain breaking
antioxidants.27 It was found from Table 1 that all the compounds
showed inhibition of ABTS+ radical. It was interesting to point
out that compounds 4a1, 4e1, 4e2, 4f1, 4f2, 4g1, 4g2, 4h1, 4h2, 4k1,
4k2, 4n1 and 4n2 exhibited better ABTS+ radical scavenging activi-
ties than the commercial synthetic antioxidant BHT, with IC50 of
31.82, 11.70, 8.24, 7.15, 5.24, 11.81, 8.47, 11.36, 8.25, 20.57,
4e1, 4f2, 4j1, 4k1, 4k2, 4m1, 4m2, and 4n2 showed better superoxide
anion radical scavenging activity than commercial synthetic anti-
oxidant BHT, with IC50 of 245.96, 237.17, 235.07, 169.14, 183.56,
153.28, 197.33, 209.10 and 146.51 lM, respectively. Unfortunately,
superoxide anion radical scavenging activities of all the com-
pounds were less than that of both BHA and ascorbic acid, while
compounds 4h1–4i2 did not exhibit superoxide anion radical scav-
enging activity. Compound 4d2 displayed very low radical scaveng-
ing activity countered by mg/mL unit in this assay, with IC50 of
11.27, 8.91 and 9.17 lM, respectively. Besides, compounds 4e1,
4e2, 4f1, 4f2, 4g1, 4g2, 4h1, 4h2, 4k2, 4n1 and 4n2 even showed
stronger radical scavenging activities than ascorbic acid in this as-
say, though all their radical scavenging activities were less than
that of BHA. Obviously, compound 4f2 exhibited the best ABTS+
radical scavenging activity, while compound 4b1 showed the low-
0.34 mg/mL, which was equivalent to 1481.85 lM. Since IC50 val-
ues of lower than 10 mg/mL indicated potent activities in antioxi-
dant properties,26 the result suggested that these compounds have
effective radical scavenging effect on superoxide anion radical gen-
eration that may help prevent or ameliorate oxidative damage.
Superoxide anion radical scavenging activities of these tested com-
pounds decreased in the order of ascorbic acid, BHA, 4n2, 4k2, 4j1,
4k1, 4m1, 4m2, 4f2, 4e1, 4b1, BHT, 4n1, 4j2, 4e2, 4g1, 4f1, 4g2, 4c2,
4c1, 4b2, 4l1, 4a2, 4l2, 4a1, 4d1, 4d2. Based on the above observation,
it could be summarized that alkyl, OH, NH, carboxylic, sulfamic and
acyl groups may have important influence on the superoxide anion
radical scavenging activities, while nitro exhibited negative effect.
The hydroxyl radical scavenging activities were also assayed in
the present work. As shown in Table 1, compounds 4f1, 4f2, 4j2, 4l1
and 4l2 showed none hydroxyl radical scavenging activities, while
all IC50 values of other compounds were less than that of both BHT
and BHA. The results demonstrated that all the compounds except
4f1, 4f2, 4j2, 4l1 and 4l2 showed better hydroxyl radical scavenging
activities than the two common antioxidants BHT and BHA. Of
these compounds, compound 4h1 displayed the best hydroxyl rad-
est. IC50 of 4b1 was found to be 1814.17 lM, which was equivalent
to 0.42 mg/mL and was clearly lower than 10 mg/mL,26 implying
good ABTS+ radical scavenging activities of these compounds.
Clearly, the order of ABTS+ radical scavenging activity of tested
was: BHA > 4f2 > 4f1 > 4e2 > 4h2 > 4g2 > 4n1 > 4n2 > 4k2 > 4h1 > 4e1 >
4g1 > ascorbic acid > 4k1 > 4a1 > BHT > 4a2 > 4b2 > 4i1 > 4i2 > 4l2 >
4c1 > 4l1 > 4m1 > 4c2 > 4m2 > 4d2 > 4j2 > 4d1 > 4j1 > 4b1. Since com-
pounds 4a1, 4e1, 4e2, 4f1, 4f2, 4g1, 4g2, 4h1, 4h2, 4k1, 4k2, 4n1 and
4n2 contained NH or OH groups, it could be concluded that NH
and OH groups were major contributors to their ABTS+ radical scav-
enging activities. In addition, methyl in 6 position of quinolone ring,
benzyl, aliphatic hydrocarbon, carboxylic, nitro, sulfamic substitu-
ents containing in Schiff-bases groups also had important influence
on their ABTS+ radical scavenging activities.
Superoxide anion radical, which is an initial radical, plays an
important role in the course of the formation of some reactive oxy-
gen species such as hydrogen peroxide, singlet oxygen and hydro-
xyl radical in organisms.3 Table 1 revealed that compounds 4b1,
ical scavenging activity, with IC50 of 244.87
much more than that of ascorbic acid (IC50 = 73.81
4n1 showed the lowest hydroxyl radical scavenging activity
lM, which was still
lM). Compound

110
Y. Zhang et al. / Bioorg. Med. Chem. Lett. 23 (2013) 107–111
14. Rousell, J.; Haddad, E. B.; Mak, J. C.; Webb, B. L.; Giembycz, M. A.; Barnes, P. J.
Mol. Pharmacol. 1996, 49, 629.
15. Ukrainets, I. V.; Gorokhova, V. O.; Benzuglyi, A. P.; Sidorenko, V. L. Farm. Zh.
2000, 1, 75.
16. Trachootham, D.; Alexandre, J.; Huang, P. Nat. Rev. Drug Discov. 2009, 8, 579.
17. Moss, R. W. Antioxidants Against Cancer; Equinox Press: New York, 2000.
18. Cornish, M. L.; Garbary, D. J. Algae 2010, 25, 155.
countered by mg/mL unit, with IC50 of 2.15 mg/mL, which was
much less than 10 mg/mL,26 suggesting effective hydroxyl radical
scavenging activities of these compounds. The radical scavenging
activity order was listed as follow: 4h1 > 4j1 > 4h2 > 4k1 > 4i1 > 4i2
> 4k2 > 4g1 > 4e2 > 4g2 > 4e1 > 4a2 > 4a1 > 4c1 > 4d1 > 4b2 > 4d2
>
4m2 > 4m1 > 4n2 > 4c2 > 4b1 > 4n1. Since these compounds 4h1–4j1,
4k1 and 4k2 exhibited better hydroxyl radical scavenging activity
than other synthetic compounds in the present study (their IC50 val-
ues were less than that of other synthetic compounds), it should be
thus concluded that NH2, nitro and sulfamic groups may be the ma-
jor contributors to their hydroxyl radical scavenging activities. In
addition, para-position of phenol in benzene ring and the presence
of carboxylic group had negative influence on the hydroxyl radical
scavenging activities and even lead to none scavenging activities on
hydroxyl radical.
In this paper, we have described the synthesis and in vitro anti-
oxidant activities of 2-oxo-quinoline-3-carbaldehyde Schiff-base
derivatives, derived from the 2-oxo-quinoline pharmacy core. Of
all these targeted compounds, compounds 4b2, 4e1, 4e2 and 4g2
showed better radical scavenging activities than BHT in DPPH as-
say; compounds 4a1, 4e1, 4e2, 4f1, 4f2, 4g1, 4g2, 4h1, 4h2, 4k1,
4k2, 4n1 and 4n2 exhibited better ABTS+ radical scavenging activi-
ties than BHT; compounds 4b1, 4e1, 4f2, 4j1, 4k1, 4k2, 4m1, 4m2,
and 4n2 displayed stronger superoxide anion radical scavenging
activities than BHT; almost all the compounds except 4f1, 4f2, 4l1
and 4l2 displayed more potent inhibition of hydroxyl radical than
both of BHA and BHT. The above results demonstrate that the ra-
tional design of 2-oxo-quinoline-3-carbaldehyde Schiff-base deriv-
atives as novel antioxidants is feasible. Further studies on the
relevant action mechanisms and problematic of the potential tox-
icity of these compounds are in progress, and will be published in
the future.
19. Gao, P.; Zhang, H. H.; Dinavahi, R.; Li, F.; Xiang, Y.; Raman, V.; Bhujwalla, Z. M.;
Felsher, D. W.; Cheng, L. Z.; Pevsner, J.; Semenza, G. L.; Dang, C. V. Cancer Cell
2007, 12, 230.
20. Liu, Z. C.; Wang, B. D.; Yang, Z. Y.; Li, Y.; Qin, D. D.; Li, T. R. Eur. J. Med. Chem.
2009, 44, 4477.
21. (a) Zhang, Y.; Zou, B. Q.; Chen, Z. F.; Pan, Y. M.; Wang, H. S.; Liang, H.; Yi, X. H.
Bioorg. Med. Chem. Lett. 2011, 21, 6811; (b) General procedure for evaluation of
DPPH radical activity: Each sample solution (0.1 mL) in DMF at different
concentrations was added to the solution [3.9 mL, 0.004% (w/v)] of DPPHÅ in
ethanol. The reaction mixture was incubated at 37 °C. The scavenging activity
on DPPHÅ was determined by measuring the absorbance at 517 nm after 30
min. All tests were performed in triplicate and mean were centred. The
scavenging activity was expressed as a percentage of scavenging activity on
DPPHÅ: SC% = [(AcontrolꢀAtest)/Acontrol)] ꢁ 100%, where Acontrol is the absorbance
of the control (DPPHÅ solution without test sample) and Atest is the absorbance
of the test sample (DPPHÅ solution plus scavenger). The control contains all
reagents except the scavenger.
22. General procedure for the preparation of compounds 2–4: The mixture of
compound 1 (15 mmol), DMF (5 mL) and POCl3 (17 mL) was refluxed at 90 °C
for 16 h. After the reaction, the mixture was poured into ice water and then
filtered to offer pale powder of compound 2. Compound 2 (10 mmol) was
treated with 70% acetic acid aqueous solution (200 mL) at 95 °C for 10 h and
then the solution was cooled to room temperature to offer needle crystals of
compound 3. The mixture of compound 3 (1 mmol), ethanol (50 mL) and
different primarily amines (1.1 mmol) or hydraziniums (1.0 mmol) was
blended together and reacted at 80 °C for 10 h. After cooling to room
temperature, powders or crystals of compound
4
were obtained; (b)
WRS-IA apparatus
Experimental: melting points were determined on
a
without correction. 1H NMR and 13C NMR spectra were recorded on
a
BRUKER AVANCE 500 spectrometer in d-DMSO. Mass spectra were recorded
on BRUKER ESQUIRE HCT spectrometer. Compound 4a1: Yields 84%, mp: 220.4–
222.3 °C; 1H NMR (500 MHz, DMSO-d6) d 12.00 (s, 1H, NH), 11.48 (s, 1H, OH),
8.27 (s, 1H, N@CH), 8.20 (s, 1H, C@CH), 7.76 (d, J = 7.9 Hz, 1H, Ar-H), 7.51 (t,
J = 7.7 Hz, 1H, Ar-H), 7.32 (d, J = 8.2 Hz, 1H, Ar-H), 7.19 (t, J = 7.5 Hz, 1H, Ar-H);
13C NMR (DMSO-d6, 125 MHz)
d 161.09, 143.67, 139.26, 134.66, 131.30,
129.11, 124.62, 122.68, 119.44, 115.54. MS m/z: 189 [M+H]+; Compound 4a2:
Yields 81%; mp: 222–224 °C; 1H NMR (500 MHz, DMSO-d6) d 11.88 (s, 1H, NH),
11.40 (s, 1H, OH), 8.20 (s, 1H, N@CH), 8.18 (s, 1H,C@CH), 7.53 (s, 1H, Ar-H), 7.34
(d, J = 8.5 Hz, 1H,Ar-H), 7.22 (d, J = 8.2 Hz, 1H, Ar-H), 2.33 (s, 3H, CH3); 13C NMR
(DMSO-d6, 125 MHz) d 160.98, 143.78, 137.33, 134.38, 132.60, 131.67, 128.46,
124.57, 119.39, 115.47, 20.82. MS m/z: 203 [M+H]+; Compound 4b1: Yields 83%,
mp: 206–208 °C; 1H NMR (500 MHz, DMSO-d6) d 12.04 (s, 1H, NH), 8.54 (s, 1H,
N@CH), 8.43 (s, 1H, C@CH), 7.82 (d, J = 7.7 Hz, 1H, Ar-H), 7.54 (t, J = 7.6 Hz, 1H,
Ar-H), 7.32 (d, J = 8.2 Hz, 1H, Ar-H), 7.20 (t, J = 7.4 Hz, 1H, Ar-H), 3.59 (t,
J = 6.7 Hz, 2H, CH2), 1.64–1.57 (m, 2H, CH2), 1.38–1.29 (m, 2H, CH2), 0.91 (t,
J = 7.4 Hz, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d 161.88, 156.21, 137.87,
136.45, 134.14, 131.36, 126.14, 123.13, 118.61, 115.90, 84.26, 33.04, 20.36,
14.19. MS m/z: 229 [M+H]+; Compound 4b2: Yields 78%, mp: 181–183 °C; 1H
NMR (500 MHz, DMSO-d6) d 11.81 (s, 1H, NH), 8.53 (s, 1H, N@CH), 8.34 (s, 1H,
C@CH), 7.59 (s, 1H, Ar-H), 7.37 (d, J = 8.4 Hz, 1H, Ar-H), 7.23 (d, J = 8.4 Hz, 1H,
Ar-H), 3.58 (t, J = 6.8 Hz, 2H, CH2), 2.33 (s, 3H, CH3), 1.63–1.56 (m, 2H, CH2),
1.38–1.29 (m, 2H, CH2), 0.91 (t, J = 7.4 Hz, 3H, CH3); 13C NMR (DMSO-d6,
125 MHz) d 161.86, 156.16, 137.92, 136.65, 133.18, 131.78, 129.02, 126.85,
119.34, 115.48, 61.17, 33.04, 20.82, 20.35, 14.18. MS m/z: 243 [M+H]+;
Compound 4c1: Yields 76%, mp:181.3–185.8 °C; 1H NMR (500 MHz, DMSO-d6) d
12.05 (s, 1H, NH), 8.71 (s, 1H, N@CH), 8.49 (s, 1H, C@CH), 7.81 (d, J = 7.8 Hz, 1H,
Ar-H), 7.54 (t, J = 7.7 Hz, 1H, Ar-H), 7.38–7.31 (5H, m, Ar-H), 7.27 (d, J = 5.5 Hz,
1H, Ar-H), 7.19 (t, J = 7.5 Hz, 1H, Ar-H), 4.80 (s, 2H, CH2); 13C NMR (DMSO-d6,
125 MHz) d 161.95, 157.24, 140.03,139.90, 137.30, 131.95, 129.82, 128.86,
128.57, 127.40,127.28, 126.87, 126.83, 122.73, 119.36, 115.51, 64.92. MS m/z:
263 [M+H]+; Compound 4c2: Yields 83%, mp:251–253 °C; 1H NMR (500 MHz,
DMSO-d6) d 12.01 (s, 1H, NH), 8.70 (s, 1H, N@CH), 8.42 (s, 1H, C@CH), 7.70 (s,
1H, Ar-H), 7.60 (s, 1H, Ar-H), 7.49 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 6.25 Hz, 2H, Ar-
H), 7.27 (d, J = 8.4 Hz, 2H, Ar-H), 4.81 (s, 2H, CH2), 2.33 (s, 3H, CH3); 13C NMR
(DMSO-d6, 125 MHz) d 161.80, 157.38, 142.54, 139.75, 137.00, 135.58, 132.24,
130.48, 129.10, 128.85, 128.55, 127.31, 126.06, 118.56, 115.82, 64.88, 20.72.
MS m/z: 277 [M+H]+; Compound 4d1: Yields 84%, mp: 22–222 °C; 1H NMR
(500 MHz, DMSO-d6) d 11.93 (s, 1H, NH), 8.52 (s, 1H, N@CH), 8.45 (s, 1H,
C@CH), 7.82 (d, J = 7.6 Hz, 1H, Ar-H), 7.54 (t, J = 8.2 Hz, 1H, Ar-H), 7.32 (d,
J = 8.2 Hz, 1H, Ar-H), 7.20 (t, J = 7.5 Hz, 1H, Ar-H), 4.62 (s, 1H, OH), 3.66 (t,
J = 2.2 Hz, 4H, 2CH2); 13C NMR (DMSO-d6, 125 MHz) d 161.95, 157.20, 139.92,
137.03, 131.80, 129.70, 126.95, 122.71, 1159.37, 115.55, 64.26, 61.23. MS m/z:
217 [M+H]+; Compound 4d2: Yields 81%, mp: 223.0–225 °C; 1H NMR (500 MHz,
DMSO-d6) d 11.96 (s, 1H, NH), 8.52 (s, 1H, N@CH), 8.37 (s, 1H, C@CH), 7.59 (s,
1H, Ar-H), 7.37 (d, J = 8.3 Hz, 1H, Ar-H), 7.23 (d, J = 8.4 Hz, 1H, Ar-H), 4.62 (s,
1H, OH), 3.65 (t, J = 2.1 Hz, 4H, 2CH2), 2.35 (s, 3H, CH3); 13C NMR (DMSO-d6,
125 MHz) d 161.85, 157.35, 137.97, 136.76, 133.18, 131.75, 128.99, 126.87,
119.32, 115.49, 64.25, 61.23, 20.83. MS m/z: 231 [M+H]+; Compound 4e1: Yields
78%, mp:251–253 °C; 1H NMR (500 MHz, DMSO-d6) d 12.14 (s, 1H, NH), 9.13 (s,
Acknowledgments
This study was supported by the China 973 Project (No.
2010CB933902; 2011CB512005; 2010CB534911), the Fund of
Guangxi Key Laboratory of Functional Phytochemicals Research
and Utilization (No. FPRU2011-6), the Guilin Scientific Research
and Technological Development Project (No. 20110106-2;
20120108-6) and the Project of State Key Laboratory Cultivation
Base for the Chemistry and Molecular Engineering of Medicinal
Resources, Ministry of Science and Technology of China
(CMEMR2011-22).
References and notes
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Y. Zhang et al. / Bioorg. Med. Chem. Lett. 23 (2013) 107–111
111
1H, OH), 8.91 (s, 2H, N@CH, C@CH), 7.83 (d, J = 7.8 Hz, 1H, Ar-H), 7.58 (t,
J = 7.7 Hz, 1H, Ar-H), 7.36 (d, J = 8.2 Hz, 1H, Ar-H), 7.25 (t, J = 7.4 Hz, 1H, Ar-H),
7.20 (d, J = 7.7 Hz, 1H, Ar-H), 7.10 (t, J = 7.7 Hz, 1H, Ar-H), 6.91 (d, J = 7.9 Hz, 1H,
Ar-H), 6.85 (t, J = 7.6 Hz, 1H, Ar-H); 13C NMR (DMSO-d6, 125 MHz) d 162.12,
153.95, 151.90, 143.01, 140.13, 138.54, 134.19, 132.31, 129.91, 128.37, 127.12,
123.01, 120.16, 119.59, 116.58, 115.74.MS m/z: 265 [M+H]+; Compound 4e2:
Yields 73%, mp: 261–263 °C; 1H NMR (500 MHz, DMSO-d6) d 12.04 (s, 1H, NH),
9.09 (s, 1H, OH), 8.90 (s, 1H, N@CH), 8.82 (s, 1H, C@CH), 7.59 (s, 1H, Ar-H), 7.41
(d, J = 9.9 Hz, 1H, Ar-H), 7.27 (d, J = 8.4 Hz, 1H, Ar-H), 7.19 (d, J = 9.3 Hz, 1H, Ar-
H), 7.10 (t, J = 7.7 Hz, 1H, Ar-H), 6.91 (d, J = 8.1 Hz, 1H, Ar-H), 6.84 (t, J = 8.1 Hz,
1H, Ar-H), 2.36 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d 161.98, 154.09,
151.90, 142.57, 138.21, 135.61, 133.65, 131.95, 130.49, 129.16, 128.28, 127.09,
120.11, 119.59, 116.57, 115.66, 20.87. MS m/z: 279 [M+H]+; Compound 4f1:
Yields 81%, mp: 265.6–267.3 °C; 1H NMR (500 MHz, DMSO-d6) d 12.12 (s, 1H,
NH), 9.61 (s, 1H, OH), 8.78 (s, 1H, N@CH), 8.61 (s, 1H, C@CH), 7.87 (d, J = 7.8 Hz,
1H, Ar-H), 7.56 (t, J = 7.7 Hz, 1H, Ar-H), 7.35 (d, J = 8.2 Hz, 1H, Ar-H), 7.22 (t,
J = 7.7 Hz, 3H, Ar-H), 6.82 (d, J = 8.6 Hz, 2H, Ar-H). 13C NMR (DMSO-d6,
125 MHz) d 162.09, 157.13, 151.99, 143.25, 140.02, 136.98, 132.00, 129.90,
127.35, 123.16, 123.06, 122.82, 119.49, 116.47, 116.35, 115.62. MS m/z: 265
[M+H]+; Compound 4f2: Yields 75%, mp: 339.8–341.7 °C; 1H NMR (500 MHz,
DMSO-d6) d 12.03 (s, 1H, NH), 9.59 (s, 1H, OH), 8.77 (s, 1H, N@CH), 8.52 (s, 1H,
C@CH), 7.63 (s, 1H, Ar-H), 7.38 (d, J = 8.3 Hz, 1H, Ar-H), 7.25 (d, J = 8.4 Hz, 1H,
Ar-H), 7.20 (d, J = 8.5 Hz, 2H, Ar-H), 6.81 (d, J = 8.6 Hz, 2H, Ar-H), 2.34 (s, 3H,
CH3); 13C NMR (DMSO-d6, 125 MHz) d 162.01, 157.08, 152.12, 143.25, 138.03,
136.70, 133.39, 131.85, 129.17, 127.16, 123.10, 123.06, 119.40, 116.37, 116.32,
115.54, 20.85. MS m/z: 279 [M+H]+; Compound 4g1: Yields 87%, mp:264.3–
265.7 °C; 1H NMR (500 MHz, DMSO-d6) d 11.91 (s, 1H, NH), 10.65 (s, 1H, NH),
8.35 (s, 1H, N@CH), 8.11 (s, 1H, C@CH), 7.78 (d, J = 7.7 Hz, 1H, Ar-H), 7.46 (t,
J = 8.3 Hz, 1H, Ar-H), 7.31 (d, J = 8.1 Hz, 1H, Ar-H), 7.24 (t, J = 7.8 Hz, 2H, Ar-H),
7.19 (t, J = 7.6 Hz, 1H, Ar-H), 7.12 (d, J = 7.7 Hz, 2H, Ar-H), 6.78 (t, J = 7.2 Hz, 1H,
Ar-H); 13C NMR (DMSO-d6, 125 MHz) d 161.51, 145.43, 138.51, 131.51, 130.26,
129.58, 128.64, 128.10, 127.22, 122.62, 120.07, 119.63, 115.56, 115.40, 112.71.
MS m/z: 264 [M+H]+; Compound 4g2: Yields 78%, mp:284.7–286.3 °C; 1H NMR
(500 MHz, DMSO-d6) d 11.80 (s, 1H, NH), 10.59 (s, 1H, NH), 8.28 (s, 1H, N@CH),
8.11 (s, 1H, C@CH), 7.56 (s, 1H, Ar-H), 7.29 (d, J = 9.5 Hz, 1H, Ar-H), 7.23 (dd,
J = 14.1, 8.0 Hz, 3H, Ar-H), 7.11 (d, J = 8.0 Hz, 2H, Ar-H), 6.78 (t, J = 7.2 Hz, 1H,
Ar-H), 2.34 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d 161.42, 145.47,
136.57, 131.70, 131.58, 131.54, 131.27, 129.58, 128.10, 127.16, 123.55, 120.02,
119.59, 115.56, 115.33, 112.69, 20.91. MS m/z: 278 [M+H]+; Compound 4h1:
Yields 76%, mp: 311.5–312.8 °C; 1H NMR (500 MHz, DMSO-d6) d 12.01 (s, 1H,
NH), 11.51 (s, 1H, NH), 8.49 (s, 1H, N@CH), 8.30 (s, 1H, C@CH), 8.16 (d,
J = 8.2 Hz, 2H, Ar-H), 7.81 (d, J = 7.3 Hz, 1H, Ar-H), 7.51 (t, J = 7.6 Hz, 1H, Ar-H),
7.34 (t, J = 9.9 Hz, 1H, Ar-H), 7.22 (d, J = 6.6 Hz, 3H, Ar-H); 13C NMR (DMSO-d6,
125 MHz) d 161.39, 150.76, 142.90, 137.12, 134.12, 133.76, 131.36, 131.13,
129.10, 126.57, 123.11, 122.80, 119.79, 115.89, 115.57, 112.03. MS m/z: 309
[M+H]+; Compound 4h2: Yields 71%, mp: 323.0–324.4 °C; 1HNMR (500 MHz,
DMSO-d6) d 11.92 (s, 1H, NH), 11.48 (s, 1H, NH), 8.42(s, 1H, N@CH), 8.28 (s, 1H,
C@CH), 8.15 (d, J = 9.2 Hz, 2H, Ar-H), 7.59 (s, 1H, Ar-H), 7.35 (d, J = 7.1 Hz, 1H,
Ar-H), 7.24 (d, J = 8.4 Hz, 3H, Ar-H), 2.35 (s, 3H, CH3); 13C NMR (DMSO-d6,
125 MHz) d 161.34, 150.78, 139.21, 139.18, 137.14, 133.66, 132.55, 131.92,
128.67, 126.58, 126.10, 124.71, 119.75, 115.73, 115.52, 112.03, 20.85. MS m/z:
323 [M+H]+; Compound 4i1: Yields 78%, mp: 339–341 °C; 1H NMR (500 MHz,
DMSO-d6) d 12.10 (s, 1H, NH), 11.87 (s, 1H, NH), 8.91 (s, 1H, N@CH), 8.88 (s, 1H,
C@CH), 8.65 (s, 1H, Ar-H), 8.39 (d, J = 12.1 Hz, 1H, Ar-H), 8.21 (d, J = 9.6 Hz, 1H,
Ar-H), 7.84 (d, J = 8.1 Hz, 1H, Ar-H), 7.57 (t, J = 7.7 Hz, 1H, Ar-H), 7.35 (d,
J = 8.2 Hz, 1H, Ar-H), 7.25 (t, J = 7.4 Hz, 1H, Ar-H).13C NMR (DMSO-d6, 125 MHz)
NH), 8.01 (s, 1H, N@CH), 7.89 (s, 1H, C@CH), 7.43 (s, 1H, Ar-H), 7.23 (d,
J = 8.3 Hz, 1H, Ar-H), 7.16 (d, J = 8.3 Hz, 1H, Ar-H), 7.09 (s, 2H, NH2), 2.29 (s, 3H,
CH3); 13C NMR (DMSO-d6, 125 MHz) d 161.45, 136.31, 132.82, 131.41, 131.27,
130.49, 127.85, 127.71, 120.00, 115.22, 20.88. MS m/z: 202 [M+H]+; Compound
4l1: Yields 87%, mp: 349–351 °C; 1H NMR (500 MHz, DMSO-d6) d 12.23 (s, 1H,
NH), 12.21 (s, 1H, COOH), 10.24 (s, 1H, C@NH), 8.51 (s, 1H, C@CH), 8.00 (d,
J = 8.4 Hz, 1H, Ar-H), 7.92 (d, J = 7.8 Hz, 1H, Ar-H), 7.66 (t, J = 7.7 Hz, 1H, Ar-H),
7.60 (d, J = 8.5 Hz, 2H, Ar-H), 7.25 (t, J = 7.5 Hz, 1H, Ar-H), 6.53 (d, J = 8.5 Hz, 2H,
Ar-H); 13C NMR (DMSO-d6, 125 MHz) d 167.92, 161.87, 157.50, 153.57, 142.90,
141.64, 138.95, 134.11, 132.27, 131.64, 126.16, 123.11, 121.47, 118.62, 117.49,
115.90, 113.07. MS m/z: 293 [M+H]+; Compound 4l2: Yields 81%, mp: 334.6–
336.6 °C; 1H NMR (500 MHz, DMSO-d6) d 12.16 (s, 1H, NH), 12.12 (s, 1H,
COOH), 10.23 (s, 1H, C@NH), 8.41 (s, 1H, C@CH), 7.68 (s, 1H, Ar-H), 7.61 (d,
J = 8.5 Hz, 1H, Ar-H), 7.49 (d, J = 8.5 Hz, 2H, Ar-H), 7.26 (d, J = 8.5 Hz, 1H, Ar-H),
6.54 (d, J = 8.5 Hz, 2H, Ar-H), 2.34 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d
167.94, 161.82, 157.47, 153.53, 142.58, 139.74, 135.60, 132.26, 131.66, 130.49,
126.03, 121.50, 119.23, 118.56, 117.46, 115.82, 113.09, 20.72. MS m/z: 307
[M+H]+; Compound 4m1: Yields 81%, mp: 298–300 °C; 1H NMR (500 MHz,
DMSO-d6) d 12.23 (s, 1H, NH), 12.08 (s, 1H, NH), 8.79 (d, J = 5.9 Hz, 2H, C@CH),
8.74 (s, 1H, N@CH), 8.51 (s, 1H, C@CH), 7.89 (d, J = 7.8 Hz, 1H, Ar-H), 7.86 (d,
J = 5.9 Hz, 2H, C@CH), 7.56 (t, J = 7.7 Hz, 1H, Ar-H), 7.35 (d, J = 8.2 Hz, 1H, Ar-H),
7.23 (t, J = 7.5 Hz, 1H, Ar-H); 13C NMR (DMSO-d6, 125 MHz) d 162.02, 161.47,
150.80, 144.52, 140.80, 139.66, 135.78, 131.85, 129.63, 125.60, 122.87, 122.01,
119.48, 115.64. MS m/z: 293 [M+H]+; Compound 4m2: Yields 76%, mp: 285.6–
286.9 °C; 1H NMR (500 MHz, DMSO-d6) d 12.21 (s, 1H, NH), 11.99 (s, 1H, NH),
8.78 (d, J = 5.1 Hz, 2H, C@CH), 8.73 (s, 1H, N@CH), 8.41 (s, 1H, C@CH), 7.85 (d,
J = 5.1 Hz, 2H, C@CH), 7.63 (s, 1H, Ar-H), 7.38 (d, J = 8.2 Hz, 1H, Ar-H), 7.25 (d,
J = 8.3 Hz, 1H, Ar-H), 2.34 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d 162.06,
161.37, 150.81, 144.66, 140.81, 137.72, 135.56, 133.25, 131.94, 128.95, 125.48,
122.03, 119.42, 115.58, 20.87. MS m/z: 307 [M+H]+; Compound 4n1: Yields 87%,
mp: 255–257 °C; 1H NMR (500 MHz, DMSO-d6) d 11.99 (s, 1H, NH), 11.63 (s,
1H, NH), 8.76 (s, 1H, N@CH), 8.28 (s, 2H, NH2), 8.09 (s, 1H, C@CH), 7.64 (d,
J = 7.8 Hz, 1H, Ar-H), 7.51 (t, J = 7.7 Hz, 1H, Ar-H), 7.31 (d, J = 8.2 Hz, 1H, Ar-H),
7.21 (t, J = 7.5 Hz, 1H, Ar-H); 13C NMR (DMSO-d6, 125 MHz) d 178.66, 161.42,
139.41, 137.29, 135.53, 131.41, 128.97, 125.83, 122.84, 119.69, 115.65. MS m/
z: 245 [MꢀH]+; Compound 4n2: Yields 84%, mp: 284.7–286.5 °C; 1H NMR
(500 MHz, DMSO-d6) d 11.91 (s, 1H, NH), 11.61 (s, 1H, NH), 8.68 (s, 1H, N@CH),
8.27 (s, 2H, NH2), 8.06 (s, 1H, C@CH), 7.42 (s, 1H, Ar-H), 7.34 (d, J = 8.4 Hz, 1H,
Ar-H), 7.22 (d, J = 8.4 Hz, 1H, Ar-H), 2.33 (s, 3H, CH3); 13C NMR (DMSO-d6,
125 MHz) d 178.61, 161.34, 137.50, 137.44, 135.36, 132.79, 131.80, 128.36,
125.68, 119.65, 115.58, 20.86. MS m/z: 259 [MꢀH]+.
23. (a) Pan, Y. M.; He, C. H.; Wang, H. S.; Ji, X. W.; Wang, K.; Liu, P. Z. Food Chem.
2010, 121, 497; (b) General procedure for evaluation of ABTS radical activity:
stock solution of ABTS (2 mM) was prepared by dissolving in phosphate
buffered saline (PBS, 50 ml) and the pH of the solution should be 7.4. ABTSÅ+
was produced by reacting of stock solution (50 ml) with K2S2O8 water solution
(200 ml, 70 mM). The mixture was left to stand in the dark at room
temperature for 15–16 h before use. For the evaluation of antioxidant
activity, the ABTSÅ+ solution was diluted with PBS to obtain the absorbency
of 0.700 0.030 at 734 nm. Compounds
4 solution (0.1 ml) at different
concentration were mixed with ABTSÅ+ solution (1.9 ml), then absorbance
was read at ambient temperature after 3 min. PBS solution was used as a blank
sample. All tests were performed in triplicate and mean were centred. The
radical scavenging activity of the sample was expressed as
SC% = [(AcontrolꢀAtest)/Acontrol] ꢁ 100%, where Acontrol is the absorbance of the
control (ABTSÅ+ solution without test sample) and Atest is the absorbance of the
test sample (ABTSÅ+ solution plus extracts).
d
161.30, 144.72, 139.73, 136.24, 131.93, 130.04, 129.81, 129.50, 125.62,
123.94, 123.42, 122.93, 119.54, 117.52, 115.86, 115.44. MS m/z: 354 [M+H]+;
Compound 4i2: Yields 65%, mp: 292–294 °C; 1H NMR (500 MHz, DMSO-d6) d
11.94 (s, 1H, NH), 11.84 (s, 1H, NH), 8.87 (s, 1H, N@CH), 8.84 (s, 1H, C@CH),
8.58 (s, 1H, Ar-H), 8.34 (d, J = 12.1 Hz, 1H, Ar-H), 8.21 (d, J = 9.6 Hz, 1H, Ar-H),
7.79 (d, J = 8.1 Hz, 1H, Ar-H), 7.48 (s, 1H, Ar-H), 7.21 (d, J = 7.4 Hz, 1H, Ar-H),
2.35 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d 161.30, 144.72, 139.73,
136.24, 131.93, 130.04, 129.81, 129.50, 125.62, 123.94, 123.42, 122.93, 119.54,
117.52, 115.86, 115.44, 20.83. MS m/z: 366 [MꢀH]+; Compound 4j1: Yields 85%,
mp:274–276 °C; 1H NMR (500 MHz, DMSO-d6) d 12.24 (s, 1H, NH), 8.50 (s, 1H,
N@CH), 7.92 (d, J = 7.8 Hz, 2H, Ar-H), 7.65 (t, J = 7.4 Hz, 1H, Ar-H), 7.57 (d,
J = 8.6 Hz, 1H, Ar-H), 7.42 (s, 2H, NH2), 7.35 (d, J = 8.3 Hz, 2H, Ar-H), 7.26 (d,
J = 8.6 Hz, 1H, Ar-H), 7.00 (s, 1H, C@CH), 6.83 (d, J = 8.7 Hz, 1H, Ar-H); 13C NMR
(DMSO-d6, 125 MHz) d 161.91, 157.86, 152.38, 142.93, 139.08, 134.16, 131.38,
130.37, 127.88, 127.80, 127.56, 123.14, 121.77, 115.89, 112.94, 112.91. MS m/
z: 328 [M+H]+; Compound 4j2: Yields 87%, mp: 289.3–290.9 °C; 1H NMR
(500 MHz, DMSO-d6) d 12.14 (s, 1H, NH), 8.40 (s, 1H, N@CH), 7.87 (d, J = 8.3 Hz,
1H, Ar-H), 7.68 (s, 2H, NH2), 7.45 (d, J = 8.6 Hz, 2H, Ar-H), 7.40 (d, J = 8.3 Hz, 1H,
Ar-H), 7.36 (s, 1H, C@CH), 6.87 (s, 1H, Ar-H), 6.59 (d, J = 8.6 Hz, 2H, Ar-H), 2.34
(s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d 161.81, 152.34, 142.55, 139.74,
135.59, 132.25, 130.48, 127.88, 127.81, 127.54, 126.05, 121.74, 118.56, 115.82,
112.95, 112.90, 20.72. MS m/z: 342 [M+H]+; Compound 4k1: Yields 68%, mp:
364.8–366.2 °C; 1H NMR (500 MHz, DMSO-d6) d 11.84 (s, 1H, NH), 8.10 (s, 1H,
N@CH), 7.90 (s, 1H, C@CH), 7.68 (d, J = 7.8 Hz, 1H, Ar-H), 7.42 (t, J = 7.7 Hz, 1H,
Ar-H), 7.28 (d, J = 8.2 Hz, 1H, Ar-H), 7.15 (t, J = 7.4 Hz, 1H, Ar-H), 7.15 (s, 2H,
NH2); 13C NMR (DMSO-d6, 125 MHz) d 161.55, 138.26, 132.60, 130.69, 129.96,
128.42, 127.79, 122.48, 120.06, 115.29. MS m/z: 188 [M+H]+; Compound 4k2:
Yields 64%, mp: 360.2–362.1 °C; 1H NMR (500 MHz, DMSO-d6) d 11.74 (s, 1H,
24. (a) Guo, T.; Wei, L.; Sun, J.; Hou, C. L.; Fan, L. Food Chem. 2011, 127, 1634; (b)
General procedure for evaluation of hydroxyl radical activity: the following
reagents were put into a reaction tube in the following order: 0.3 ml of 20 mM
sodium salicylate, 1.0 ml of 1.5 mM ferrous sulfate, 1.0 ml of various
concentrations of sample solution, 0.7 mL of 6 mM H2O2. They were mixed
immediately, and then the reaction tubes were put in the 37 °C water bath for
1 h, the absorbance of the mixture was recorded at 510 nm against a blank.
Ascorbic acid was used as the positive control. All tests were performed in
triplicate and mean were centred. The hydroxyl radical-scavenging ability was
calculated as follows: hydroxyl radical-scavenging activity (%) = [(A0ꢀA1)/
A0] ꢁ 100%, where A0 is the absorbance without samples and A1 the
absorbance in the presence of the samples.
25. (a) Marklund, S.; Marklund, G. Eur. J. Biochem. 1974, 47, 469; (b) Zhao, F.; Liang,
H.; Cheng, H.; Wang, J. Acta Chim. Sinica 2011, 69, 925; (c) General procedure
for evaluation of superoxide anion radical activity: under room temperature, to
4.5 mL of 0.05 M Tris–HCl buffered solution, 1.0 mL of sample in DMF solution
(in different concentration) and 0.4 mL of 30 mM 1,2,3-trihydroxybenzene
solution were added and reacted for 5 min. Then 0.5 mL of 8.0 M hydrochloric
acid solution was added and the absorbance of the mixture was recorded at
320 nm against a blank. All tests were performed in triplicate and mean were
centred. The superoxide anion radical-scavenging ability was calculated as
follows: superoxide anion radical-scavenging activity (%) = [(A0ꢀA1)/
A0] ꢁ 100%, where A0 is the absorbance without samples and A1 the
absorbance in the presence of the samples.
26. Lee, Y. L.; Yen, M. T.; Mau, J. L. Food Chem. 2007, 104, 1.
27. Leong, L. P.; Shui, G. Food Chem. 2002, 76, 69.