An efficient carbodiimide-mediated synthesis and dna-binding studies of novel 2-chloro/mercapto-quinoline-fused 1,3-thiazolidinones via one-pot three-component condensation

Article abstract of DOI:10.1080/17415990903295678

A new and efficient method for the preparation of 2-(2-chloroquinolin-3-yl)-3-(4-methylphenyl)-1, 3-thiazolidin-4-one derivatives has been assembled by DCC:-mediated three-component one-pot reaction of amine, aldehyde, and mercaptoacetic acid. The final compounds were obtained in quantitative yields within 50 min. The synthesized compounds were characterized by elemental analysis, FT-IR, ¹H-NMR, and mass spectral data. The selected compounds were studied for interaction with calf thymus DNA by electronic spectra, viscosity measurements as well as thermal denaturation studies. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K_b) had a value of 5.3 × 10⁵ M^-1 for 2a and 5.8 × 10⁵ M^-1 for 3a. The viscosity measurements indicated that the viscosity of sonicated rod-like DNA fragments increased.

Full text of DOI:10.1080/17415990903295678

This article was downloaded by: [Gazi University]
On: 08 January 2015, At: 07:28
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Sulfur Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gsrp20
An efficient carbodiimide-mediated
synthesis and DNA-binding studies of
novel 2-chloro/mercapto-quinoline-
fused 1,3-thiazolidinones via one-pot
three-component condensation
Devappa S. Lamani a , K. R. Venugopala Reddy a , H. S. Bhojya
Naik a , H. R. Prakash Naik a & L. R. Naik b
a Department of PG Studies and Research in Industrial
Chemistry, School of Chemical Sciences , Kuvempu University ,
Shankaraghatta, 577 451, Karnataka, India
b Department of Physics , Karnataka University , Dharwad, 580
003, India
Published online: 12 Oct 2009.
To cite this article: Devappa S. Lamani , K. R. Venugopala Reddy , H. S. Bhojya Naik , H. R. Prakash
Naik & L. R. Naik (2010) An efficient carbodiimide-mediated synthesis and DNA-binding studies
of novel 2-chloro/mercapto-quinoline-fused 1,3-thiazolidinones via one-pot three-component
condensation, Journal of Sulfur Chemistry, 31:1, 49-59, DOI: 10.1080/17415990903295678
To link to this article: http://dx.doi.org/10.1080/17415990903295678
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.

This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Sulfur Chemistry
Vol. 31, No. 1, February 2010, 49–59
An efficient carbodiimide-mediated synthesis and DNA-binding
studies of novel 2-chloro/mercapto-quinoline-fused
1,3-thiazolidinones via one-pot three-component condensation
Devappa S. Lamania, K.R. Venugopala Reddya*, H.S. Bhojya Naika, H.R. Prakash Naika
and L.R. Naikb
aDepartment of PG Studies and Research in Industrial Chemistry, School of Chemical Sciences, Kuvempu
University, Shankaraghatta, 577 451 Karnataka, India; bDepartment of Physics, Karnataka University,
Dharwad 580 003, India
(Received 18 May 2009; final version received 23 August 2009)
A new and efficient method for the preparation of 2-(2-chloroquinolin-3-yl)-3-(4-methylphenyl)-1,
3-thiazolidin-4-one derivatives has been assembled by DCC:-mediated three-component one-pot reaction
of amine, aldehyde, and mercaptoacetic acid. The final compounds were obtained in quantitative yields
within 50 min. The synthesized compounds were characterized by elemental analysis, FT-IR, 1H-NMR,
and mass spectral data. The selected compounds were studied for interaction with calf thymus DNA by
electronic spectra, viscosity measurements as well as thermal denaturation studies. On binding to DNA,
the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (Kb) had
a value of 5.3 × 105 M−1 for 2a and 5.8 × 105 M−1 for 3a. The viscosity measurements indicated that the
viscosity of sonicated rod-like DNA fragments increased.
Keywords: quinoline; DCC; thiazolidinones; one-pot synthesis; DNA binding; viscosity measurements;
thermal denaturation
1. Introduction
The pharmacological properties of quinoline and their derivatives attracted worldwide attention
in the last few decades because of their wide occurrence in natural products and drugs (1).
Literature survey revealed that five- to six-membered heterocyclic compounds containing one or
two heteroatoms fused to a quinoline ring in a linear fashion were found to possess anti-tumor,
anti-cancer, anti-HSV (2), anti-convulsion (3), and anti-inflammatory (4) activities. On the other
hand, thiadiazoles, in general, and 1,3-thiadiazoles, in particular, have variety of applications
in medicine. The heterocycles have various pharmacological and biological activities, namely
COX-1 inhibitors (2), inhibitors of the bacterial enzyme MurB (3), non-nucleoside inhibitors of
HIV-RT (4), and anti-histaminic agents (5). Consequently, many different protocols that allow
the synthesis of 1,3-thiazolidinones skeletons have been developed.
*Corresponding author. Email: venurashmi30@rediffmail.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2010 Taylor & Francis
DOI: 10.1080/17415990903295678
http://www.informaworld.com

50 D.S. Lamani et al.
These methods employ a one-pot three-component condensation or a two-step synthesis (6).
The reaction is believed to proceed via imine formation in the first step followed by an attack of a
sulfur nucleophile on the imine carbon and finally intramolecular cyclization with the elimination
of water. The latter step seems to be critical for obtaining high yields of 2-(2-chloroquinolin-3-yl)-
3-(4-methylphenyl)-1,3-thiazolidin-4-one. Therefore, variations have been made in the removal
of water during the cyclization. In addition, there are scattered reports of using anhydrous ZnCl2
or sodium sulfate as a desiccant (7). In all the above-mentioned methods, the reaction requires
prolonged heating at a high temperature (90–100 ◦C) for nearly 12–15 h. In order to circumvent
these difficulties, we have chosen a radically different approach to generate 1,3-thiazolidin-4-one
scaffolds by simpler methods in quantitative yields. The protocol is ideally suited for the synthesis
of a thiazolidinone library (8).
The literature survey reveals that there is evidence to infer that the anti-tumor activity is due
to the intercalation between the base pairs of DNA and interferences with the normal functioning
of enzyme topoisomerase II, which is involved in the breaking and releasing of DNA strands
(9). The anti-tumor drugs that intercalate DNA are of growing interest in the field of anti-cancer
drugs. Particularly, they are characterized by planar chromospheres, which are often constituted
by three or four condensed rings, which can intercalate into base pairs. Results of the various
binding studies have been useful in designing new and promising anti-cancer agents (10). The
DNA-binding studies of pyrimidothienoquinolines have been recently reported (11, 12).
In continuation of our research program (3, 13–17) toward the synthesis of potentially bioactive
quinoline molecules, we made an attempt to report an efficient method for the synthesis of novel
2-chloro/mercapto-quinoline-fused 1,3-thiazolidinones derivatives, via one-pot three-component
condensation. The sulfur-containing molecule has advantages, such as easy preparation derivati-
zation, and biological impotents; the DNA-binding studies indicate compounds 2a and 3a when
they bind with base pairs of calf thymus DNA (CT-DNA).
2. Results and discussion
The chemistry using amine, aldehyde, and mercaptoacetic acid proceeded uneventfully and the
product was isolated in a quantitative yield after work-up. To optimize the ratio of reactants,
experiments were carried out using different proportions of the reactants. It was observed that the
ratio of reactants at 1:2:3 for amine, aldehyde, and mercaptoacetic acid, respectively, gave almost
quantitative yields. This is in agreement with the earlier observation reported by Homes et al. (18).
In a typical experiment, amine and aldehyde were stirred in THF under ice cooling for 15–20 min,
followed by the addition of mercaptoacetic acid and DCC and the reaction mixture is stirred for
an additional 50–55 min. The DCC, which was precipitated, was removed by filtration and the
usual work-up gave the desired products in almost quantitative yields. We have observed that
the addition of DCC in ice-cold conditions gives better yields when compared with the reaction
carried out at refluxion in a water bath and ambient room temperature.
Our mechanistic investigations using spectral studies gave proof of cyclized products. IR spectra
of the compound 2a/3a showed the carbonyl stretching frequency at 1625–1660 cm−1. This
confirms the subsequent cyclization of compound 1, by removal of CHO present at the 3-position
of the quinoline nucleus. Further, the structure assigned was confirmed by 1H-NMR spectra that
− −
show doublet peak at 3.72–3.76 ppm due to fused 1,3-thiazolidinones ( S CH2) (2a)/(3a). The
resonate singlet at 12.26–12.24 ppm corresponds to tautomeric form of SH proton of compound
3a, signal exhibits multiplets at 7.13–7.78 ppm for aromatic protons. The mass spectral results
show molecular ion peak at m/z = 339[M+] for 2a and 338 [M + H] for 3a, respectively (Table 1,
Scheme 1) (13, 19–22).

Table 1. Physical and analytical data of 2-(2-chloro/mercapto-quinolin-3-yl)-3-(4-methylphenyl)-1,3-thiazolidin-4-one derivatives.
Analysis calculated (found) (%)
Compound
Color
Yield (%)
m.p. (◦C)
Crystal solvent
Molecular formula (mol/wt)
C
H
N
S
2a
2b
2c
2d
3a
3b
3c
3d
Yellowish
Yellowish orange
Yellowish
Yellowish orange
Orange solid
Yellowish orange
Yellowish orange
Orange solid
79
89
82
84
79
69
74
67
215–217
198–200
225–227
192–194
232–236
210–213
225–227
205–208
Ethanol
Ethanol
Ethanol
Ethanol
Ethyl acetate
Ethyl acetate
Ethanol
C18H13ClN2OS (340.8)
C19H15ClN2OS (354.8)
C19H15ClN2O2S, (370.8)
C19H15ClN2OS, (354.8)
63.43 (63.53)
64.31 (64.23)
64.31 (64.23)
61.53 (61.46)
63.83 (63.77)
64.74 (64.70)
61.93 (61.87)
64.74 (64.70)
3.84 (3.74)
4.26 (4.32)
4.26 (4.32)
4.08 (4.02)
4.17 (4.21)
4.58 (4.61)
4.38 (4.44)
4.58 (4.61)
8.22 (8.28)
7.89 (7.78)
7.89 (7.78)
7.55 (7.58)
8.28 (8.22)
7.95 (7.89)
7.60 (7.55)
7.95 (7.89)
9.41 (9.49)
9.04 (9.09)
9.04 (9.09)
8.65 (8.72)
C
18H13N2OS2, (338.4)
18.95 (18.90)
18.19 (18.24)
17.40 (17.34)
18.19 (18.24)
C19H16N2OS2, (352.47)
C19H16N2O2S2, (368.47)
C19H16N2OS2, (352.47)
Ethyl acetate

52 D.S. Lamani et al.
O
N
O
H2N
R
R
DCC/THF
Ice 0–5 °C
Amines
H
S
2
Cl
+
N
1
Cl
N
OH
R1
R1
HS
2a–d
Aldehydes
O
Mercapto acids
3
Na2S/Con. HCl
ethanol
O
N
O
R
R
H2N
H
S
DCC/THF
Ice 0–5 °C
+
5
SH
N
SH
3a–d
N
R1
OH
R1
HS
Mercapto quinoline
4
R= H, CH3 OCH3
R1 = CH3
O
6
Scheme 1. Synthesis of 2-(2-chloro/mercapto-quinolin-3-yl)-3-(4-methylphenyl)-1,3-
thiazolidin-4-one derivatives.
2.1. DNA-binding studies (absorption spectral studies)
The application of electronic absorption spectroscopy in CT-DNA-binding studies is one of the
most important techniques (13). The binding of the molecules to DNA has been well character-
ized by the large hypochromism. After intercalation, the π∗ orbital of compounds could couple
with π orbital of base pairs, thus decreasing the π∗ → π transition of energy and resulting
bathochromism. Hence, the decrease in the absorption intensity and significant red shift due to
stacking interaction between drug and CT-DNA (14). The DNA-binding studies were character-
ized by absorbance maximum at 298 nm for 2a and 302 nm for 3a. The addition of increasing
higher concentration of DNA led to hypochromic and bathochromic (red shift) changes in its
visible absorption spectra as a result of formation of more stable complexes (Figures 1 and 2).
The interaction of 2a and 3a with CT-DNA resulted in the decrease of absorption intensity accom-
panied by a shift toward higher wavelengths (∼3 and 5 nm). Around 12–9% reduction intensity
of absorption was observed at 298 and 302 nm peak maximum in the presence of an excess of
CT-DNA. The lowest value observed in spectral changes (including red shift and hypochromic-
ity) was used to evaluate intrinsic binding constant (Kb); its observed value of 5.3 × 105 M−1 for
2a and 5.8 × 105 M−1 for 3a from the spectral result suggested that compound 2a binds more
strongly with base pairs than 2d (Table 2) (15, 16, 23–26).

Journal of Sulfur Chemistry 53
0.9
0.5
0.1
7
6
5
4
3
2
1
A
B
C
1
2
3
4
5
6
DNA concentration
292.7
527.6
nm
762.4
Figure 1. UV-absorption spectra in Tris–HCl buffer upon addition of CT-DNA (2a) [DNA] = 0.5 and 10 μm, drug, 20,
30, 40, and 50 μm. Arrow shows the absorbance changing upon the increase of DNA concentration.
0.9
0.24
0.22
0.20
0.18
0.16
0.14
0.12
0.10
0.08
0.06
A
B
C
0.01 0.02 0.03 0.04 0.05 0.06
DNA concentration
0.6
0.0
297.1
423.5
nm
550.0
Figure 2. UV-absorption spectra in Tris–HCl buffer upon addition of CT-DNA (3a) [DNA] = 0.5 and 10 μm, drug, 20,
30, 40, and 50 μm. Arrow shows the absorbance changing upon the increase of DNA concentration.

54 D.S. Lamani et al.
Table 2. Absorption spectral properties of compounds 2a and 3a bound to
CT-DNA.
Compound
λmax (nm)
Kb (M−1
)
Tm (◦C)
2a
3a
298
302
5.3 × 105
5.8 × 105
69
65
1.18
1.16
1.14
1.12
1.10
1.08
1.06
Compound (2a)+[DNA]
Compound (3a)+[DNA]
0.1
0.2
0.3
0.4
0.5
0.6
0.7
Compound (2a) and (3a)/[DNA]
Figure 3. Effect of increasing amount of 2a and 3a on the relative viscosities of CT-DNA at 25 ◦C.
2.2. Viscosity measurements
For further clarification, the interaction modes of 2a and 3a with DNA were investigated by
viscosity measurements. An increase in the viscosity of native DNA is regarded as a diagnostic
feature of an intercalation process (17, 24). We have measured the viscosity changes in short,
rod-like DNA fragments. The relative length increase (L/L0) of the complex formed between
2a, 3a and DNA is shown in Figure 3. It is evident that the binding of 2a and 3a increased the
viscosity of DNA corresponding to an increase in the contour length of the DNA fragments. In
order to elucidate the binding mode of the present compound, the viscosity measurements were
carried out on CT-DNA by varying the concentration of added compounds. The effects of the
compounds on the viscosity of rod-like DNA were shown (Figure 3). The presence of compound
had an obvious effect on the relative viscosity of CT-DNA with an increase in concentration of
the added compounds (17).
2.3. Thermal denaturation
Other strong evidence for the intercalative binding of 2a and 3a into the double-helix DNA was
obtained from DNA melting studies. The intercalation of small molecules into the double helix
is known to increase the DNA melting temperature (Tm), at which the double helix denatures
into a single-stranded DNA, owing to the increased stability of the helix in the presence of an
intercalator (13). The molar extinction coefficient of DNA bases at 260 nm in the double helical
form is much less than the single-stranded form; hence, melting of the helix leads to an increase in
the absorbance at 260 nm. The DNA melting studies were carried out with CT-DNA in the absence

Journal of Sulfur Chemistry 55
1.25
1.20
1.15
1.10
1.05
1.00
[DNA]
(2a)/[DNA]
(3a)/[DNA]
0
20
40
60
80
100
Temperature °C
Figure 4. Melting curves of CT-DNA in the presence and absence of 2a and 3a.
and presence of 2a and 3a. Tm (melting temperature) for CT-DNA was 60 5 ◦C in the absence of
compounds, but in the presence of 2a and 3a, the Tm of CT-DNA increased by 7–10 ◦C (Table 1).
These variations in DNA melting temperature strongly supported the intercalation of compounds
into the double-helix DNA (Figure 4) (16, 26).
3. General synthesis
3.1. Synthesis of 2-(2-chloroquinolin-3-yl)-3-phenyl-1, 3-thiazolidin-4-one (2a)
The appropriate amine (1.0 mmol) and aldehyde (2.0 mmol) were stirred in THF under ice-cold
conditions for 15 min, followed by an addition of mercaptoacetic acid (3.0 mmol). After 5 min
DCC (1.2 mmol) was added to the reaction mixture at 0–5 ◦C and the reaction mixture stirred for an
additional 50 min at room temperature. DCC was removed by filtration and the filtrate was concen-
trated to dryness under reduced pressure and the residue was taken up in ethyl acetate. The organic
layer was successively washed with 15% aq. acetic acid, water, 12% aq. sodium hydrogen carbon-
ate, and then finally with brine. The organic layer was dried over sodium sulfate and solvent was
removed under reduced pressure to get a crude product that was purified by column chromatogra-
phyonsilicagelusingethylacetate-CHCl3 asaneluent. Similarly, thesameprocedurewasusedfor
all the quinoline derivatives. This compound was obtained as an yellowish solid in 79% yield; IR
1
cm−1 (KBr) 2931 (Ar CH), 1660 (C O), 1399, 1291, 1158, 894, 747, 687. H-NMR (400 MHz,
−
=
−
− −
CDCl3) 6.39 (s, 1H, thiazolidin ring CH), 3.72–3.76 (d, J = 9.65 Hz, S CH2), 7.13–7.45 (m,
+
−
−
5H, Ar CH, quinoline), 7.61–7.83 (m, 5H, Ar CH, phenyl ring). FAB mass m/z = 339(M ).
3.2. Synthesis of 2-(2-chloro-6-methylquinolin-3-yl)-3-phenyl-1, 3-thiazolidin-4-one (2b)
This compound was obtained as an yellowish orange solid in 89% yield; IR cm−1 (KBr)
1
−
=
2932 (Ar CH), 1662 (C O), 1397, 1293, 1158, 894, 745, 686. H-NMR (400 MHz, CDCl3)
−
− −
6.40 (s, 1H, thiazolidin ring CH), 3.72–3.76 (d, J = 9.64 Hz, S CH2), 2.34 (s, 3H, CH3),
−
−
7.13–7.45 (m, 4H, Ar CH, quinoline), 7.61–7.83 (m, 5H, Ar CH, phenyl ring). FAB mass
m/z = 355[M + H].

56 D.S. Lamani et al.
3.3. Synthesis of 2-(2-chloro-6-methoxyquinolin-3-yl)-3-phenyl-1, 3-thiazolidin-4-one (2c)
This compound was obtained as an yellowish solid in 82% yield; IR cm−1 (KBr) 2932 (Ar CH),
−
1
=
1662 (C O), 1398, 1293, 1155, 893, 747, 686. H-NMR (400 MHz, CDCl3) 6.40 (s, 1H,
−
− −
thiazolidin ring CH), 3.72–3.74 (d, J = 9.64 Hz, S CH2), 3.98 (s, 3H, OCH3), 7.13–7.44 (m,
−
−
4H, Ar CH, quinoline), 7.61–7.84 (m, 5H, Ar CH, phenyl ring). FAB mass m/z = 370[M+].
3.4. Synthesis of 2-(2-chloro-8-methylquinolin-3-yl)-3-phenyl-1,3-thiazolidin-4-one (2d)
This compound was obtained as an yellowish orange solid in 89% yield; IR cm−1 (KBr) 2931
1
−
=
(Ar CH), 1660 (C O), 1399, 1291, 1158, 894, 747, 687. H-NMR (400 MHz, CDCl3) 6.36 (s,
−
− −
−
1H, thiazolidin ring CH), 3.71–3.73 (d, J = 9.64 Hz, S CH2), 7.18–7.45 (m, 4H, Ar CH,
−
quinoline), 7.62–7.88 (m, 5H, Ar CH, phenyl ring). FAB mass m/z = 355[M + H].
3.5. Synthesis of 2-(2-mercaptoquinolin-3-yl)-3-phenyl-1,3-thiazolidin-4-one (3a)
This compound was obtained as orange solid in 79% yield; IR cm−1 (KBr) 2926 (Ar CH), 2756
−
1
−
−
=
( SH ), 1626 (C O), 1399, 1290, 1158, 894, 743, 686. H-NMR (400 MHz, CDCl3) 12.22 (s,
−
− −
1H, SH), 6.32(s, 1H, thiazolidinring CH), 3.63–3.70(d, J = 9.64 Hz, S CH2), 7.19–7.44(m,
−
−
5H,Ar CH, quinoline), 7.53–7.74 (m, 5H,Ar CH, phenyl ring). FAB mass m/z = 339[M + H].
3.6. Synthesis of 2-(2-mercapto-6-methylquinolin-3-yl)-3-phenyl-1,3-thiazolidin-4-one (3b)
This compound was obtained as an yellowish orange solid in 69% yield; IR cm−1 (KBr) 2922
1
−
−
−
=
(Ar CH), 2752 ( SH ), 1626 (C O), 1399, 1290, 1156, 895, 747, 684. H-NMR (400 MHz,
−
CDCl3) 12.22 (s, 1H, SH), 6.33 (s, 1H, thiazolidin ring CH), 3.62–3.69 (d, J = 9.65 Hz,
− −
−
−
S CH2), 7.19–7.44 (m, 4H,Ar CH, quinoline), 2.42 (s, 3H, CH3), 7.53–7.74 (m, 5H,Ar CH,
phenyl ring). FAB mass m/z = 353[M + H].
3.7. Synthesis of 2-(2-mercapto-6-methoxyquinolin-3-yl)-3-phenyl-1,3-thiazolidin-4-
one (3c)
This compound was obtained as an yellowish orange solid in 74% yield; IR cm−1 (KBr) 2926
1
−
−
−
=
(Ar CH), 2756 ( SH ), 1626 (C O), 1398, 1291, 1158, 894, 748, 687. H-NMR (400 MHz,
−
CDCl3) 12.21 (s, 1H, SH), 6.33 (s, 1H, thiazolidin ring CH), 3.63–3.69 (d, J = 9.65 Hz,
− −
−
S CH2), 7.19–7.44 (m, 4H, Ar CH, quinoline), 3.06 (s, 3H, OCH3), 7.53–7.74 (m, 5H,
+
−
Ar CH, phenyl ring). FAB mass m/z = 368[M ].
3.8. Synthesis of 2-(2-mercapto-8-methylquinolin-3-yl)-3-phenyl-1,3-thiazolidin-4-one (3d)
This compound was obtained as orange solid in 69% yield; m.p, 205–208◦C; IR cm−1 (KBr) 2926
1
−
−
−
=
(Ar CH), 2756 ( SH ), 1626 (C O), 1398, 1292, 1158, 893, 747, 688. H-NMR (400 MHz,
−
CDCl3) 12.22 (s, 1H, SH), 6.32 (s, 1H, thiazolidin ring CH), 3.63–3.70 (d, J = 9.65 Hz,
− −
−
−
S CH2), 7.18–7.42 (m, 4H,Ar CH, quinoline), 2.34 (s, 3H, CH3), 7.51–7.74 (m, 5H,Ar CH,
phenyl ring). FAB mass m/z = 353[M + H].

Journal of Sulfur Chemistry 57
4. Conclusion
The synthetic route adopted for the synthesis of quinoline derivatives (2a/3a) was very efficient
and gave a good yield. The efficient and simple methodology was based on the DCC-catalyzed
synthesis, and the efficiency of the employed methodology can be explained by the fact that energy
required is probably much less than the activation energy necessary for each reaction, so that the
reaction rate is increased. DNA-binding studies indicate hypochromicity and bathochromic shifts
of compounds 2a and 3a when they bind with base pairs of CT-DNA. The binding constant values
of 5.3 × 105 M−1 for 2a and 5.8 × 105 M−1 for 3a suggested that the compound 3a bind more
avidly with CT-DNA than 2a.
5. Experimental
All organic solvents used for the synthesis were of analytical grade. The thin-layer chro-
matography (TLC) was performed on Baker-Flex silica gel 1B-F (1.55) plates using ethyl
acetate and petroleum ether (1:8). Melting points were determined on a Mel-Temp appara-
tus and were uncorrected. IR spectra were recorded in the matrix of KBr with Perkin-Elmer
1430 spectrometer. 1H-NMR spectra were recorded on Jeol spectrometer (400 MHz), and
chemical shifts (δ) given in ppm relative to the trimethylsilyl or tetramethylsilane (TMS)
in CDCl3 solvent. Mass spectra were recorded by electron ionization on a Finnigan MAT
312 spectrometer. C, H, and N analyses were performed at Cochin University, Sophis-
ticated Test & Instrumentation Center, Kochi, Kerala, India. Ammonium hexafluorophos-
phate (NH4PF6) was purchased from Qualigens (India). Tris–HCl buffer (5 mM Tris–HCl,
=
50 mM NaCl, pH 7.2, Tris Tris(hydroxymethyl) amino methane) solution was prepared using
deionized double distilled water. CT-DNA was purchased from Bangalore Gene, Banga-
lore, India. Ultraviolet-visible (UV–VIS) absorption spectra were determined in a Perkin-
Elmer model 554 and UV–VIS recording spectrophotometer using quartz cuvettes of 10 mm
path light.
5.1. UV–VIS absorption studies
The concentration of CT-DNA per nucleotide [C(p)] was measured using its known extinction
coefficient at 260 nm (6600 M−1 cm−1) (27). The absorbance at 260 nm (A260) and 280 nm (A280
)
for CT-DNA was measured to check purity. The ratio A260/A280 was found to be 1.8:1.9, indi-
cating that CT-DNA was satisfactorily free from protein. A buffer (5 mM tris(hydroxymethyl)
aminomethane, pH 7.2, 50 mM NaCl) was used for the absorption, viscosity, and thermal
denaturation experiments.
Absorption titration experiments were carried out by varying the DNA concentration
(0–100 μM) and maintaining the compound concentration constant (30 μM). Absorption spectra
were recorded after each successive addition of DNA and equilibration (approximately 10 min).
For both the compounds 2a and 3a, observed data were then fit into Equation (1) in order to obtain
the intrinsic binding constant, Kb (28):
[DNA]
[DNA]
1
=
+
,
(1)
(εa − εf )
(εb − εf ) Kb(εa − εf )
where εa, εf , and εb are the apparent, free, and bound compound extinction coefficients at 298 nm
(2a) and 302 nm (3a), respectively. A plot of [DNA]/(εa − εf ) versus [DNA] gave a slope of

58 D.S. Lamani et al.
1/(εb − εf ) and an intercept y equal to 1/Kb(εb − εf ), where Kb is the ratio of the slope to the
intercept y.
5.2. Viscosity measurements
Viscosity measurements were carried out using a semimicro-dilution capillary viscometer at room
temperature. Each experiment was performed three times and an average flow time was calculated.
Data were presented as (η/ηo) versus binding ratio, where η is the viscosity of DNA in the presence
of complex and ηo is the viscosity of DNA alone (29).
5.3. Thermal denaturation
Melting studies were carried out by monitoring the absorption of CT-DNA (50 μM) at 260 nm
at various temperatures in the presence (5–10 μM) and absence of each complex. The melting
temperature (Tm) at which 50% of the double-stranded DNA becomes single-stranded and the
curve width (σT), the temperature range between 10% and 90% noticed absorption increases
occurred and calculated as reported (30).
Acknowledgements
D.S.L. thanks the Indian Institute of Science, Bangalore, and Karnataka University, Dharwad, for providing spectral data
and Cochin University, Sophisticated Test & Instrumentation Center, Kochi, Kerala, for the elemental analysis facility,
and we also thank Kuvempu University for awarding a research fellowship.
References
(1) Selvi, S.T.; Mohan, P.S. Spectrosc. Lett. 2002, 35, 439–445.
(2) Toth, J.; Blasko, G.; Dancso, A.; Toke, L.; Nyerges, M. Synth. Commun. 2006, 36, 3581–3589.
(3) (a) Raghavendra, M.; Bhojya Naik, H.S.; Sherigara, B.S. Arkivoc 2006, 15, 153–159; (b) Prakash Naik, H.R.; Bhojya
Naik, H.S.; Ravikumar Naik, T.R.; Raja Naik, H.; Lamani, D.S.; Aravind, T. J. Sulfur Chem. 2008, 29, 583–592.
(4) Loaiza-Rodriguez, P.; Quintero, A.; Rodríguez-Sotres, R.; Solano, J.D.; Lira-Rocha, A. Eur. J. Med. Chem. 2004,
39, 5–10.
(5) Gawande, N.G.; Shingare, M.S. Indian J. Chem. 1987, 26B, 387–389.
(6) Brickner, S.J.; Hutchinson, D.K.; Barbachyn, M.R.; Manninen, M.N.; Ulanowicz, D.A.; Garmon, S.A.; Grega, K.C.;
Hendges, S.K.; Troops, D.S.; Ford, C.W.; Zurenko, G.E. J. Med. Chem. 1996, 39, 673–679.
(7) Look, G.C.; Schullek, J.R.; Homes, C.P.; Chinn, J.P.; Gordon, E.M.; Gallop, M.A. Bioorg. Med. Chem. Lett. 1996,
6, 707–712.
(8) Singh, M.P.; Joseph, T.; Kumar, S.; Lown, J.W. Chem. Res. Toxicol. 1992, 5, 597–607.
(9) TilakaRaj, T.; Ambekar, S.Y. J. Chem. Res. 1988, 50, 537–551.
(10) TilakaRaj, T.; Ambekar, S.Y. J. Chem. Eng. Data 1988, 33, 530–531.
(11) Thulstrup, P.W.; Thormann, T. Biochem. Biophy. Res. Commun. 1999, 254, 416–421.
(12) Barreca, M.L.; Chimirri, A.; Luca, L.D.; Monforte, A.; Monforte, P.; Rao, A.; Zappala, M.; Balzarini, J.; De Clercq,
E.; Pannecouque, C.; Witvrouw, M. Bioorg. Med. Chem. Lett. 2001, 1793–1796.
(13) (a) Lamani, D.S.; Venugopala Reddy, K.R.; Bhojya Naik, H.S.; Savyasachi, A.; Naik, H.R. Nucleos. Nucleot.
Nucl. Acids 2008, 27, 1197–1210; (b) Prakash Naik, H.R.; Bhojya Naik, H.S.; Ravikumar Naik, T.R.; Naik, H.R.;
Raghavendra, M.; Aravinda, T.; Lamani, D.S. Phosphorus Sulfur Silicon Relat. Elem. 2009, 184, 2109–2114.
(14) (a) Nandeshwarappa, B.P.; Aruna Kumar, D.B.; Bhojya Naik, H.S.; Mahadevan, K.M. J. Sulfur Chem. 2005, 27,
373; (b) Ramesh, S.; Bhojya Naik, H.S.; Harish Kumar, H.N. J. Sulfur Chem. 2007, 28, 573–579.
(15) Nandeshwarappa, B.P.;ArunaKumar, D.B.; Kumaraswamy, M.N.; RaviKumar,Y.S.; BhojyaNaik, H.S.; Mahadevan,
K.M. Phosphorus Sulfur Silicon. Relat. Elem. 2006, 181, 1545–1556.
(16) (a) Lamani, D.S.; Venugopala Reddy, K.R.; Bhojya Naik, H.S.; Prakash Naik, H.R.; Sridhar, A.M. J. Macromol.
Sci., Part A 2008, 45, 857–864; (b) Shahabuddin, S.; Gopal, M.; Sathees, M.; Raghavan, C. J. Cancer. Mol. 2007, 3,
139–146.
(17) (a) Prakash Naik, H.R.; Bhojya Naik, H.S.; Ravikumar Naik, T.R.; Raja Naik, H.; Lamani, D.S.;Aravind, T. J. Sulfur
Chem. 2008, 29, 583–592; (b) Prabhakara, M.C.; Basavaraju, B.; Bhojya Naik, H.S. Bioinorg. Chem. Appl. 2007,
320, 3649.
(18) Homes, C.P.; Chinn, J.P.; Look, C.G.; Gordon, E.M.; Gallop, M.A. J. Org. Chem. 1995, 60, 7328–7333.

Journal of Sulfur Chemistry 59
(19) Diurno, M.V.; Mazzoni, O.; Calignano, P.E.; Giordano, F.; Bolognese, A. J. Med. Chem. 1992, 35, 2910–2912.
(20) Singh, S.P.; Parmar, S.S.; Raman, K.; Stenberg, V.I. Chem. Soc. Rev. 1981, 81, 175–203.
(21) Srivastava, S.K.; Srivastava, S.L.; Srivastava, S.D. J. Indian Chem. Soc. 2000, 77, 93–104.
(22) Sharma, R.C.; Kumar, D. J. Indian Chem. Soc. 2000, 77, 492–494.
(23) (a) Patel, D.J. Acc. Chem. Res. 1979, 12, 118–125; (b) Zuby, G.L. Biochemistry, 2nd ed.; McMillan: New York,
1988; pp 217–236.
(24) McCoubery, A.; Latham, H.C.; Cook, P.R.; Rodger, A.; Lowe, G. FEBS Lett. 1996, 380, 73–78.
(25) Li, G.G.; Wang, H.M.; Li, A.Z., Eds. Molecular Biophysical Chemistry; Higher Education Publisher: Beijing, 1992;
pp 276–328.
(26) Fairley, T.A.; Tidwell, R.R.; Donkor, I.; Naiman, N.A.; Ohemeng, K.A.; Lombardy, R.J.; Bentley, J.A.; Cory, M.J.
J. Med. Chem. 1993, 36, 1743–1746.
(27) Reichmann, M.E.; Rice, S.A.; Thomas, C.A.; Doty, P. J. Am. Chem. Soc. 1954, 76, 3047–3053.
(28) Wolfe, A.; Shimer, G.H.; Meehan, T. Biochemistry 1987, 26, 6392–6398.
(29) Raja, A.; Rajendiran, V.; Maheswari, P.U. J. Inorg. Biochem. 2005, 99, 1717–1732.
(30) Zhang, H.; Liu, C.S.; Bu, X.H.; Yang, M. J. Inorg. Biochem. 2005, 99, 1119–1125.