Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies

Article abstract of DOI:10.1007/s12039-013-0541-4

New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards β-tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of β-tubulin.

Full text of DOI:10.1007/s12039-013-0541-4

c
J. Chem. Sci. Vol. 126, No. 1, January 2014, pp. 205–212. ꢀ Indian Academy of Sciences.
Synthesis of new biphenyl-substituted quinoline derivatives,
preliminary screening and docking studies
NELLISARA D SHASHIKUMAR1,∗, GANGANAIKA KRISHNAMURTHY1,
HALEHATTI S BHOJYANAIK2, MAYASANDRA R LOKESH1 and
KAGINALLI S JITHENDRAKUMARA1
1Department of Chemistry, Sahyadri Science College, Shimoga 577 451, India
2Department of PG Studies and Research in Industrial Chemistry, School of Chemical Sciences,
Kuvempu University, Shankaraghatta 577 451, Shimoga, India
e-mail: shashikumarnd@gmail.com
MS received 6 April 2013; revised 10 September 2013; accepted 18 September 2013
Abstract. New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H
NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic
activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concen-
tration values showed promising inhibiting activity and are potent biological agents. The compounds showed
minimum binding energy towards β-tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards
the active pocket and may be considered as a good inhibitor of β-tubulin.
Keywords. Quinoline biphenyl; antioxidant; anthelmintic; docking; β-tubulin.
1. Introduction
2. Experimental
Quinoline is a heterocyclic scaffold of paramount All the reagents and solvents were used as received
importance to living beings. Several quinoline deriva- from commercial suppliers, unless otherwise stated. All
tives isolated from natural resources or prepared syn- chemicals used for the synthesis were of analytical
thetically are significant with respect to medicinal grade or laboratory grade and purchased from HiMe-
chemistry and biomedical use. The bark of Cinchona dia Laboratories Pvt. Ltd., Sigma Chemical Co., USA,
plant (also known as Jesuit’s or Cardinal’s bark) con- E Merck, Germany, Sarabhai Merck Company, India,
taining quinine was utilized to treat palpitations,1,2 and specialty chemicals were procured as samples
fevers and tertians, since more than 200 years. The from commercial suppliers in India. All equipments
compounds containing the quinoline motif are most were inspected visually for cleanliness and integrity
widely used as antimalarials,3 antibacterials,4 antifun- before use. Mass spectra of the synthesized compounds
gals,5 and anticancer agents.6 Additionally, quinoline were recorded on Agilent 6320 Ion Trap mass spectro-
derivatives find use in the synthesis of fungicides, viru- meter. IR spectra were recorded on a Shimadzu IR-
1
cides, biocides, alkaloids, rubber chemicals and flavour- 470 spectrometer. H NMR spectra were recorded on
ing agents.7 They are also used as polymers, catalysts, a Bruker DRX-300 Avance spectrometer (300 MHz).
corrosion inhibitors, preservatives and as solvents for Melting point was determined using a Buchi melting
resins and terpenes. Furthermore, these compounds find point B-540 model and are uncorrected.
applications in transition metal catalysis for uniform
polymerization and luminescence chemistry.8,9 Owing
2.1 Synthesis of biphenyl derivatives 4a–b
to this, the synthesis of substituted quinolines has been
a subject of great focus in organic chemistry.
The compounds 4a and 4b were synthesized by the
literature methods.10–14
2.2 Synthesis of quinoline derivatives 6, 7a, 7b
The product 2-chloro-3-formylquinoline 6 synthesized
by the reported methods and the compound 6 was
∗For correspondence
205

206
Nellisara D Shashikumar et al.
converted to 7a by hydrolysing the –Cl group by distillation was stirred with 10 mL of distilled water for
refluxing with aqueous acetic acid. The compound 30 min. The solid so obtained was filtered and sepa-
7b was obtained by treating the compound 6 with rated, washed with 10 mL of distilled water and dried in
Na2S/DMF.15,16
an oven under reduced pressure for 5 h at 50◦C.
2.4a 4ꢁ-[2-Oxo-3-([1,2,4]triazol-4-yliminomethyl)-
2H-quinolin-1-ylmethyl]-biphenyl-2-carboxylic acid:
IR: 3413, 1763, 1701 and 1616 cm−1 for –OH, C=O
2.3 General procedure for the synthesis of 11a, 11c,
13a and 13c
1
The compounds 7a/7b (20 mmol), were mixed with
20 mmol of bromomethylbiphenyl-2ꢁ-carboxylic acid
methyl ester 4a and 20 mmol of K2CO3 in 20 mL DMF
was stirred for 2–3 h at room temperature. After the
reaction, it was poured into crushed ice. The separated
solid was filtered and washed with 100 mL water. The
obtained precipitate (10 mmol) and 10 mmol of corre-
sponding amines were dissolved in 20 mL of methanol
and refluxed for 4–5 h. Progress of the reaction was
monitored by TLC (methanol : MDC in 2 : 8 ratio).
After completion of the reaction, it was poured into
ice-cold water (50 mL) and the solid separated was fil-
tered and used without purification for the next step.
The obtained solid was dissolved in methanol (25 mL)
and mixed with a solution of 25 mmol KOH in 20 mL of
water. The reaction mixture was refluxed for 2 h. Then,
the methanol was distilled off. To the reaction mixture,
30 mL of distilled water was added and acidified to pH
3–4 using 0.1N HCl solution. Filtered the solid, washed
with 10 mL of water and dried in an oven under reduced
pressure for 5 h at 50◦C.
and C=N, respectively. H-NMR (300 MHz, DMSO-
d6): δ 7.3–8.7 (m, 16H, Ar-H and -HC=N-), 4.25
(s, 2H, -CH2-Ar), 11.8 (s, 1H, -COOH). 13C NMR
400 MHz, DMSO-d6: δ 169.4 (-COOH), 164.5 (C=O),
163.7 (C=N), 148.0 (triazole C=N), 120–140 (Ar),
47.7 (-CH2-N).
2.4b 4ꢁ-{2-Oxo-3-[(4-[1,2,4]triazol-1-ylmethyl-phenyl-
imino)-methyl]-2H-quinolin-1-ylmethyl}-biphenyl-2-
carboxylic acid: IR: 3403, 1758.3, 1698 and
1618 cm−1 for –OH, C=O and C=N, respectively.
1H-NMR (300 MHz, DMSO-d6): δ 7.3–8.7 (m, 20H,
Ar-H and -HC=N-), 4.25 (s, 2H, -CH2-Ar), 4.9 (s,
2H, -CH2-triazole), 11.9 (s, 1H, -COOH). 13C NMR
400 MHz, DMSO-d6: δ 164.1 (C=O), 163.5 (tetrazole
C), 163.7 (C=N), 148.0 (triazole C=N), 120–140 (Ar),
47.7 (-CH2-N).
2.4c 1-[2ꢁ-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-
3-([1,2,4]triazol-4-yliminomethyl-1H-quinolin-2-one:
IR: 3465, 1710, 1698 and 1618 cm−1 for NH and
1
C=N, respectively. H-NMR (300 MHz, DMSO-d6):
2.4 General procedure for synthesis of 11b, 11d, 13b
and 13d
δ 6.9–8.5 (m, 16H, Ar-H and -HC=N-), 4.22 (s, 2H,
-CH2-Ar), 5.6 (b, 1H, -NH). 13C NMR 400 MHz,
DMSO-d6: δ 169.4 (-COOH), 164.1 (C=O), 153.5
(C=N), 143.6 & 151.3 (triazole C=N), 120–146 (Ar),
55.7 & 47.7 (-CH2-).
A solution of the compound 7a/7b (20 mmol)
is stirred with bromomethylbiphenyl-2ꢁ-(N-triphenyl-
methyl)tetrazole 4b (20 mmol) and K2CO3 (20 mmol)
in 20 mL of DMF at room temperature for 2–3 h. The
reaction mixture was poured into crushed ice, filtered
and washed to get intermediate. The obtained precipi-
tate (10 mmol) was dissolved in 20 mL of methanol
and 10 mmol of corresponding amines was added. The
resulting mixture was refluxed for 4–5 h. The reaction
was monitored by TLC (methanol : MDC in 2 : 8
ratio). After completion of the reaction, it was poured
into ice-cold water (50 mL) and filtered. The product
was used without purification for the next step. The
obtained product was dissolved in 20 mL of methanol
and refluxed with 25 mmol of aqueous KOH, the com-
pletion of reaction checked by TLC (methanol : MDC
in 1 : 10 ratio). After completion of the reaction,
1N HCl (5 mL) was added and refluxed for 2 h. The
solid obtained after the complete removal of solvent by
2.4d 1-[2ꢁ-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-
3-[(4-[1,2,4]triazol-1-ylmethyl-phenylimino)-methyl]-
1H-quinolin-2-one: IR: 3445, 1710, 1698 and
1
1618 cm−1 for NH and C=N, respectively. H-NMR
(300 MHz, DMSO-d6): δ 7.2–8.6 (m, 20H, Ar-H and
-HC=N-), 4.18 (s, 2H, -CH2-Ar), 4.82 (s, 2H, -CH2-
triazole), 5.75 (b, 1H, -NH). 13C NMR 400 MHz,
DMSO-d6: δ 164.1 (C=O), 163.5 (tetrazole C), 153.5
(C=N), 143.6 & 151.3 (triazole C=N), 120–140 (Ar),
47.7 (-CH2-N).
2.4e 4ꢁ-[3-([1,2,4]Triazol-4-yliminomethyl)-quinolin-
2-ylsulphanylmethyl]-biphenyl-2-carboxylic acid: IR:
3415, 1770, 1705 and 1612 cm−1 for –OH, C=O and

Quinoline biphenyl derivatives
207
1
Br
C=N, respectively. H-NMR (300 MHz, DMSO-d6):
δ 6.9–8.4 (m, 16H, Ar-H and -HC=N-), 4.32 (s, 2H,
-CH2-Ar), 11.2 (s, 1H, -COOH). 13C NMR 400 MHz,
DMSO-d6: δ 169.4 (-COOH), 160.8 (S-C=N ring),
157.0 (C=N), 148.2 (triazole C=N), 121.3–148.7 (Ar),
38.5 (-CH2-S).
aq. methanol
AcOH
Br2
COOMe
4a
Br
Pd(OAc)2, TEA,
TPP, Acetonitrile
CN
Br
+
CN
B(OH)2
NaN3
DMF
1
2
3
N
N
2.4f 4ꢁ-{3-[(4-[1,2,4]triazol-1-ylmethyl-phenylimino)-
methyl]-quinolin-2-ylsulphanylmethyl}-biphenyl-2-
carboxylic acid: IR: 3403, 1758, 1698 and 1618 cm−1
for –OH, C=O and C=N, respectively. 1H-NMR
(300 MHz, DMSO-d6): δ 7.2–8.6 (m, 20H, Ar-H and
-HC=N-), 4.42 (s, 2H, -CH2-Ar), 4.85 (s, 2H, -CH2-
triazole), 11.74 (s, 1H, -COOH), 13C NMR 400 MHz,
DMSO-d6: δ 163.5 (tetrazole C), 160.6 (S-C=N ring),
157.2 (C=N), 148.6 & 151.3 (triazole C=N), 120–148
(Ar), 38.5 (-CH2-S).
N
KOH,
Methanol
Cl -CPh3
Br2AcOH
N
CPh3
4b
Scheme 1. Synthetic scheme of biphenyl derivatives.
reacted with sodium azide in DMF to give the tetrazole
derivative, which on protecting the tetrazole –NH with
triphenylmethyl chloride and followed by bromination
yields the product 4b.
2-Chloro-3-formylquinoline (6) has been synthe-
sized by Vilsmeier–Haack reaction using acetanilide,
POCl3/DMF (scheme 2).14–16 Functional group trans-
formation of formyl group can be used to get new
derivatives. The product 6 was converted to 7a by
acid hydrolysis of the –Cl group. On treating 6 with
Na2S/DMF, substitutes the –Cl group with –SH group
giving the product 7b (scheme 2).
The product 7a was converted into new Schiff base
derivatives (11a–d) by condensation with biphenyl
derivatives (4a, b) in K2CO3/DMF, followed by dif-
ferent amines in ethanol and then deprotection of car-
boxylic acid by base-catalysed hydrolysis in aque-
ous alcohol (scheme 3). Similarly, the product 7b
was converted to products 13a–d, except the deprotec-
tion of tetrazole is done by acid-catalysed hydrolysis
(scheme 4).
2.4g {2-[2ꢁ-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl-
sulphanyl]-quinolin-3-ylmethylene}-[1,2,4]triazol-4-yl-
amine: IR: 3340, 1703 and 1611 cm−1 for NH and
1
C=N, respectively. H-NMR (300 MHz, DMSO-d6):
δ 7.0–8.5 (m, 16H, Ar-H and -HC=N-), 4.34 (s, 2H,
-CH2-Ar), 5.3 (b, 1H, -NH). 13C NMR 400 MHz,
DMSO-d6: δ 169.1 (-COOH), 160.6 (S-C=N ring),
160.1 (C=N), 143.6 (triazole C=N), 121.3–148.7 (Ar),
55.7 (-CH2-triazole), 38.5 (-CH2-S).
2.4h {2-[2ꢁ-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl-
sulphanyl]-quinolin-3-ylmethylene}-(4-[1,2,4]triazol-1-
ylmethyl-phenyl)-amine: IR: 1655, 1709 and
1
3410 cm−1 for C=N and NH, respectively. H-NMR
(300 MHz, DMSO-d6): δ 7.3–8.5 (m, 20H, Ar-H and
-HC=N-), 4.48 (s, 2H, -CH2-Ar), 4.78 (s, 2H, -CH2-
triazole), 5.67 (b, 1H, -NH). 13C NMR 400 MHz,
DMSO-d6: δ 163.5 (tetrazole C), 160.6 (S-C=N
ring), 160.1 (C=N), 143.6 & 151.3 (triazole C=N),
122–148.7 (Ar), 55.7 (-CH2-triazole), 38.5 (-CH2-S).
Structures of the obtained products were confirmed
by elemental analysis, IR, H NMR and mass spec-
1
tral data. The IR spectrum of the compounds 11a–
d recorded as KBr pellet, showed two peaks between
1700 and 1640 cm−1 for –C=N– (outside the ring) and
the absence of ring –C=N– stretching frequency con-
forms N-alkylation. Compounds 13a–d showed two
peaks between 1700 and 1600 cm−1 for –C=N– of
inside ring and outside the ring. Also, the absence of
3. Results and discussion
Biphenyl derivatives (4a, b) were synthesized aldehyde group frequency in the range of 1700 cm−1
by Suzuki coupling reaction10–13 of 2-cyano-1- gave an account of the formation of Schiff base.
bromobenzene (1) with 4-methylphenyl boronic
The proton NMR spectra of the compounds recorded
acid (2) in presence of palladium acetate- in CDCl3/DMSO-d6 showed a singlet peak at 12–
triphenylphosphine, in basic condition (TEA) and 10 ppm due to the carboxylic acid proton, a broad peak
acetonitrile as solvent to give product 3 (scheme 1). between 4 and 6 ppm confirms the presence of tetra-
The product 4ꢁ-methylbiphenyl-2-carbonitrile 3, was zole –NH. The biphenyl-substituted two methylic pro-
hydrolysed in acidic condition to produce the 4ꢁ- tons appear in the range of 3–4 ppm as a singlet. The
methylbiphenyl-2-carboxylic acid, followed by bromi- mass spectra of the compounds showed molecular ion
nation gives the product 4a. Also, the product 3 was peak M+ at [M+1] m/z values corresponding to the

208
Nellisara D Shashikumar et al.
CHO
OH
CHO
O
aq.AcOH
reflux
N
N
H
CHO
POCl3
7a
DMF
N
Cl
NHCOCH3
CHO
SH
Na2S
DMF
6
5
N
7b
Scheme 2. Synthesis of quinoline derivatives.
Br
N
N
CHO
O
R
CHO
O
O
R
N
R1
+
R
N
H
7a
4a,b
10a,b
11a - d
where 4 or 10 a = -COOH, b =
N
,
N
N
R
R1
N
N
H
N
11a
-COOH
N
H2
N
N
N
N
N
N
11b
11c
11d
N
N
H
H2N
N
N
N
-COOH
H2
N
N
N
N
N
N
N
N
H
H2
N
Scheme 3. Synthesis of N-biphenyl quinoline derivatives.
R1
Br
N
CHO
N
S
N
S
CHO
SH
+
R
N
R
13a − d
12 a,b
R
7b
4a,b
N
where 4 or 10 a = -COOH, b =
,
N
R
R1
N
N
N
H
N
N
N
11a
11b
11c
11d
-COOH
N
H2N
N
N
N
N
N
H
H2N
N
N
N
N
-COOH
H2N
N
N
N
N
N
N
H
H2
N
Scheme 4. Synthesis of S-biphenyl quinoline derivatives.

Quinoline biphenyl derivatives
209
Table 1. Physical properties, analytical data and mass spectral data of compounds 11a–d and 13a–d.
Sl.
No.
%
yield∗
M.P.
(in ◦C)
Elemental analysis
H
M/z
value
Compound
C
N
1
2
3
4
5
6
7
8
11a
11b
11c
11d
13a
13b
13c
13d
67.8
72.3
65.2
42.3
53.6
81.2
50.2
63.7
171–173
152–154
120–122
154–156
119–122
95–97
69.39 (69.48)
73.49 (73.46)
65.87 (65.95)
70.25 (70.32)
67.12 (67.08)
71.32 (71.33)
63.86 (63.79)
68.41 (68.37)
4.28 (4.26)
4.63 (4.67)
3.95 (4.04)
4.53 (4.47)
4.10 (4.11)
4.61 (4.53)
4.02 (3.91)
4.39 (4.35)
15.56 (15.58)
12.90 (12.98)
26.68 (26.62)
22.31 (22.37)
14.98 (15.04)
12.56 (12.60)
25.59 (25.75)
21.73 (21.75)
450.5
540.6
474.5
564.6
466.5
556.6
490.5
580.6
101(dec.)
182–184
∗Percentage yield, are on the basis of the final product
molecular weight. Table 1 contains the data of elemen- comparing the zone of inhibition, the selected com-
tal analysis, m/z values, melting point and percentage pounds were checked for their MIC (minimum inhibi-
yields of the synthesized compounds.
tion concentration) values. The MIC values of less than
30 μg/mL are shown in table 3. It is observed that, most
of the samples showed promising activity. The com-
pounds 11d and 13d with two traizole rings have been
considered as good inhibitors.
3.1 Antimicrobial activity
Antibacterial activity carried out by well diffusion
method using nutrient agar medium, DMSO as control
and chloramphenicol is used as a standard bactericide.
Antifungal activity was carried out by well diffusion
3.2 Antioxidant activity
method using potato dextrose agar (PDA) medium, Antioxidant activity of the synthesized derivatives was
DMSO as control and fluconazole is used as a standard evaluated using the DPPH free radical scavenging assay
fungicide.17–19 Biological properties of the synthesized by standard methods.20,21 Data given in table 4 re-
compounds are screened for bacterial and fungal strains presents the DPPH free radical scavenging activity of
(tables 2 and 3). Most of the synthesized compounds the prepared compounds 11a–d and 13a–d. All the
showed inhibition property against the strains used. compounds showed scavenging activity of more than
Among the test samples, 11b and 13a showed more 50%. Thus, the compounds are good antioxidant agents,
activity when compared to the standards used. After which are capable of reacting with a free radical.
Table 2. Antimicrobial activity – zone of inhibition.
Zone of inhibition (mm)
Sl.
Antibacterial
Antifungal
No Comp. S. aureus B. subtilis S. typhi E. coli S. coccus C. albicans A. niger
1
2
3
11a
11b
11c
2
8
5
6
7
6
9
6
6
5
12
7
7
11
5
7
8
7
11
10
6
4
5
6
11d
13a
13b
5
9
6
9
10
8
6
7
9
11
6
5
10
11
7
9
10
5
9
11
7
7
8
9
10
11
13c
–
–
08
–
2
3
07
–
8
9
10
–
4
6
7
6
–
08
0
6
5
–
09
0
13d
11
10
–
12
09
–
Std1.∗
Std2.#
DMSO
0
0
0
0
0
∗Chloramphenicol, #Fluconazole

210
Nellisara D Shashikumar et al.
Table 3. Antimicrobial activity – minimum inhibition concentration.
MIC of the compounds (μg/mL)
Sl.
Antibacterial
Antifungal
No Comp. S. aureus B. subtilis S. typhi E. coli S. coccus C. albicans A. niger
1
2
3
4
5
6
11a
11b
11d
13a
13b
13d
–
20
–
15
–
21
17
12
10
13
25
30
–
–
–
–
30
09
14
25
–
27
17
19
15
29
14
22
21
13
17
21
30
12
14
19
16
25
27
–
29
12
Table 4. Antioxidant activity by DPPH radical scavenging method.
Sl.
% scavenging activity at different concentrations (μg/mL)
No.
Compounds
25
50
100
250
500
1
2
3
4
5
6
7
8
9
11a
11b
11c
11d
13a
13b
13c
13d
BHT*
12.25
07.81
10.52
39.63
12.86
10.23
06.32
25.15
12.35
24.25
18.62
21.85
53.35
21.56
22.83
12.52
40.32
25.72
56.87
30.54
54.23
80.48
32.79
33.56
21.83
60.58
58.51
71.83
41.53
61.28
91.56
42.13
51.23
34.54
93.64
86.25
81.76
65.23
78.75
97.51
56.52
62.81
49.42
98.25
94.32
*Butylated hydroxytoluene
Among them, 11d and 13d were more active when com- rial (figure 2). It is clear that all the newly synthesized
pared to the standard BHT. The graphical representation
of antioxidant activity is given in figure 1.
compounds exhibit more activity than the standard,
against the earthworms used. Concentration of test sam-
ples and the standard used was 10 mg/mL in DMF. The
impact of most of the compounds was more than that
of standard. Activity may occur due to the presence of
more potential quinoline, triazole and tetrazole rings in
3.3 Anthelmintic activity
Results of anthelmintic activity of synthesized com-
pounds are given in table 5. Graphical representation of the compounds. Procedure for anthelmintic activity is
anthelmintic activity is given as supplementary mate-
supplied as Supplementary information.
Figure 1. DPPH free radical scavenging activity.

Quinoline biphenyl derivatives
3.4 Docking studies
211
Table 5. Anthelmintic activity.
Time (min)
Paralysis
In correlation to in vitro anthelmintic activity, it is
thought worthwhile to carry out in silico studies to
support the in vitro activity. Automated docking was
used to assess the orientation of inhibitors bound in
the active pockets of β-tubulin(PDB ID: 1OJ0). Molec-
ular docking of selected ligands molecules with β-
tubulin revealed that all the compounds have exhibited
better docking score when compared to the standard
albendazole. Procedure for docking is supplied as
Supplementary information.
Compounds
Pin pinch
Death
1
2
3
4
5
6
7
8
9
11a
11b
11c
11d
13a
13b
13c
13d
12.07
24.00
13.45
17.34
21.50
12.34
14.00
11.50
18
15.00
28.45
21.00
25.49
27.00
22.00
22.54
16.00
25.00
28.50
42.00
28.00
29.50
36.00
40.50
25.00
24.00
28.20
Albendazole
Among the newly synthesized molecules 11a, 11c,
13c and 13d have showed a good in vitro activity and
docking score with β-tubulin protein. The compounds
11a, 11c, 13c and 13d have showed maximum bind-
ing affinity with the −241.95, −251.30, −286.69 and
−289.96 kJ mol−1, respectively. These docking scores
are considered as good inhibitor of β-tubulin when
compared to the standard drug albenzazole which is
−199.31 kJ mol−1, the values obtained in docking studi-
es are tabulated in table 6.
(standard)
DMF
10
18.39
32.47
46.08
Results showed that the synthesized compounds have
less energy compared to the standard drugs, which sug-
gest that synthesized compounds have excellent affinity
towards the target protein.
4. Conclusion
The new compounds 11a–d and 13a–d were pre-
pared by simple transformation and coupling reactions.
The obtained products were characterized by elemental
analysis, IR, NMR and mass spectral data. The synthe-
sized compounds were screened for antimicrobial acti-
vity at the MIC level and in vitro antioxidant activity
as well as anthelmintic activity. The compounds 11d
and 13d showed more activity, which can be attributed
to the triazole and tetrazole rings. All the compounds
are potent towards the activities carried out. Docking
study of the synthesized compounds was done with
β-tubulin protein. All the compounds showed good
docking scores.
Figure 2. Anthelmintic activity.
Supplementary information
Table 6. Docking scores.
The supplementary information can be seen at www.ias.
Docking Score
ac.in/chemsci.
Sl. No.
Compounds
Etotal (kJ mol−1
)
Acknowledgements
1
2
3
4
5
11a
11c
13c
−241.95
−251.30
−286.69
−289.96
−199.31
Authors are thankful to the Department of Industrial
Chemistry, Kuvempu University, Shimoga, Manage-
ment and staff of Alkem Laboratories Ltd., R&D cen-
ter, Bangalore, Karnataka, India, Sri. Venkateshwara
13d
Albenzazole

212
Nellisara D Shashikumar et al.
Industries and Mandli Industrial Estate, Shimoga for
providing necessary facilities.
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