P. J. Bindu et al. / Bioorg. Med. Chem. Lett. 22 (2012) 898–900
899
O
H
HO
R
pUC19 DNA diminish gradually, whereas Form II increases. Under
comparable experimental conditions, oximes (Fig. 2), exhibit more
effective DNA cleavage activity compared to halogen derivatives.
Further studies in detail are currently underway to clarify the
mechanism.
Supercoiled DNA was completely converted to nicked and linear
DNA at the concentrations of 80 lM (3d–i). But, in the same run
N
N
O
H
b
Cl
3a-Ni
N
Cl
2a
the halogen derivatives are not completely converted to nicked
and linear DNA (3a–c). Higher concentrations were not examined
because of the precipitation of oximes in the reaction mixture. This
reveals that QOE are capable to accelerate the cleavage of plasmid
DNA dramatically, which may be due to the electron donating
groups and further studies in detail are currently underway to clar-
ify the cleavage mechanism.
In conclusion, we have reported the simple, convenient and
high yielding synthesis of 2-chloro-3-formyl quinoline oxime es-
ters. The electrophoretic data of 2-chloro-3-formyl quinoline
oxime esters showed concentration and substitution dependent
nucleolytic activities. The electron donating groups are highly reac-
tive radical. These radicals abstracts hydrogen atoms efficiently at
C-40 of 2-deoxyribose in B-DNA. The molecules having halogen and
nitro groups are less active. The generated nitrogen and oxygen
radical are capable to accelerate the cleavage of plasmid DNA in
halogen and nitro substituted QOE.
Scheme 2. Synthesis of quinoline oxime esters. Reagents and condition: (b) RCOCl,
Et3N, CH2Cl2, 0 °C.
Table 1
Synthesis of quinoline oxime esters
a
Entry
R
Time (h)
Yieldb (%)
Mp (°C)
3a
3b
3c
3d
3e
3f
3g
3h
3i
C6H5
1
1
1
1
1
1
1
1
1
92
92
75
88
95
90
95
85
92
169–171
156–158
162–164
159–161
180–182
149–151
150–152
150–152
148–150
p-OCH3C6H4
p-OHC6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
p-FC6H4
o-FC6H4
m-dinito-C6H3
a
All the products were characterised by elemental analysis, 1H NMR, 13C NMR
and mass spectral data.
b
Yields of isolated products.
Acknowledgments
One of the authors (Bindu) thankful to Indian Institute of sci-
ence, Bangalore for providing facilities to carry out the biological
activity and for NMR and mass spectra.
Supplementary data
Figure 1. Photo cleavages of DNA by QOE were irradiated with UV light at 365 nm.
Supercoiled DNA runs at position I (SC) and nicked DNA at position II (NC). Lane 1:
Supplementary data associated with this article can be found, in
control DNA (with out compound), Lane 2: 40
l
M (3a), Lane 3: 40
M (3e), Lane 7: 40
M (3i).
l
M (3b), Lane 4:
40
40
l
l
M (3c), Lane 5: 40
M (3g), Lane 9: 40
l
M (3d), Lane 6: 40
l
l
lM (3f), Lane 8:
lM (3h), Lane 10: 40
References and notes
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Figure 2. Light-induced cleavage of DNA by QOE of 80 lM were irradiated with UV
light at 365 nm. Supercoiled DNA runs at position I (SC), linear DNA at position III
(LC) and nicked DNA at position II (NC). Lane 1: control DNA (with out compound),
Lane 2: 80
Lane 6: 80
l
l
M (3a), Lane 3: 80
M (3e), Lane 7: 80
l
l
M (3b), Lane 4: 80
M (3f), Lane 8: 80
l
M (3c), Lane 5: 80
l
l
M (3d),
M (3h),
lM (3g), Lane 9: 80
Lane 10: 80 lM (3i).
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Chem. Lett. 2005, 15, 1525; (c) General procedure for the preparation of quinoline
oxime: To a solution of 2-chloro-3-formyl quinolline (2 g, 49.0 mmol) in EtOH
(30 mL) was added hydroxylamine hydrochloride (2.2 g, 64.0 mmol) and Et3N
(5.0 mL, 64.0 mmol) at room temperature. After being stirred for 1 h, the
were irradiated for 2 h, in 1:9 DMSO/Trisbuffer (20 lM, pH 7.2) at
365 nm. Cleaving ability was determined quantitatively by the
effectiveness in converting super coiled plasmid DNA (Form I) to
nicked circular (Form II) as shown in Figures 1 and 2, at the concen-
tration of (40, 80 lM). In Figure 2, control experiments did not show
any apparent cleavage of DNA (lane 1). The studies show that the
synthesized oxime esters can be induced to photoextrusion under
conditions required for DNA cleavage producing intermediates
capable of hydrogen abstraction. With increasing concentration of
respected derivatives (lanes 2 and 3), the amount of Form I of