Synthesis and Antimicrobial Activity of Novel Bis-1,2,3-triazol-1H-4-yl-substituted Aryl Benzimidazole-2-thiol Derivatives

Article abstract of DOI:10.1134/S1070363220080186

Abstract: Novel bis-1,2,3-triazol-1H-4-yl-substitutedaryl benzimidazole-2-thiol derivatives have been synthesized from 5-methoxy and5-difluoromethoxy bis-propargyl substituted benzimidazole-2-thiols using the“click chemistry,” tested for their antimicrobi

Full text of DOI:10.1134/S1070363220080186

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 8, pp. 1501–1506. © Pleiades Publishing, Ltd., 2020.
Synthesis and Antimicrobial Activity
of Novel Bis-1,2,3-triazol-1H-4-yl-substituted Aryl
Benzimidazole-2-thiol Derivatives
Y. Aparnaa, G. Nirmalab, N. J. P. Subhashinib, L. N. Sharadab,*, and Sivan Sreekanthb
a Matrusri Engineering College, Saidabad, Telangana, Hyderabad, 500059 India
b Department of Chemistry, Osmania University, Telangana, Hyderabad, 500007 India
*e-mail: aparnayeddala@gmail.com
Received January 28, 2020; revised July 12, 2020; accepted August 1, 2020
Abstract—Novel bis-1,2,3-triazol-1H-4-yl-substituted aryl benzimidazole-2-thiol derivatives have been synthe-
sized from 5-methoxy and 5-difluoromethoxy bis-propargyl substituted benzimidazole-2-thiols using the “click
chemistry,” tested for their antimicrobial activity and subjected to molecular docking studies. Structures of the
compounds have been elucidated from IR, NMR, and mass spectra.
Keywords: benzimidazole-2-thiol, propargyl bromide, azide, click reaction, antimicrobial activity, molecular
docking
DOI: 10.1134/S1070363220080186
INTRODUCTION
Antimicrobial activity. Antimicrobial activity
of the products was tested using the microtitre broth
dilution method measuring zone of inhibition in mm.
The newly synthesized compounds 5a–5l were tested
in vitro at concentration of 10 μg/mL for their activity
against Escherichia coli, Salmonella typhi, Pseudomonas
aeruginosa, and Staphylococcus aureus. Standard
antibacterial drug ciprofloxacin (10 μg/mL) was used
as a standard. Each experiment was carried out in
triplicates, and the average reading was recorded. The
results of antibacterial activity are expressed in terms of
zone of inhibition (Table 1). 90% Of growth inhibition
was considered as MIC of the compound as per standard
protocol. Triazole derivatives 5a–5l were dissolved in
DMSO at 10 μg/mL concentration. The inhibition zones
were measured at the end of an incubation period of
18 h at 37°C.
2-Mercapto benzimidazoles are well known as
biologically and pharmacologically active compounds
[1–4]. 1,2,3-Triazole derivatives [5–7] containing
2-mercapto benzimidazoles have been anticipated as
promising pharmacophores. In the present study synthesis
of such new derivatives was carried out by using the
“click chemistry” [8]. The products were tested for their
antimicrobial activity.
RESULTS AND DISCUSSION
Synthesis of 5-(difluoromethoxy)-1H-benzimidazole-
2-thiol and 5-methoxy-1H-benzo[d]imidazole-2-thiol
was based on the known procedure [9, 10]. S- and
N-bis propargylation of these compounds were also
carried out according to the reported method [11]. The
structures of bis propargylated compounds 3a, 3b were
confirmed by 1H and 13C NMR and mass spectra. In 1H
NMR spectrum of compound 3a the signal recorded at
3.72 ppm was attributed to the methylene group attached
to sulfur atom and the singlet at 4.42 ppm corresponded
to the methylene attached to nitrogen atom. Following
coupling of semiproducts 3a, 3b with azides 4a–4f led
to bis triazolyl-substituted arylbenzimidazole-2-thiol
derivatives 5a–5l (Scheme 1) via the “click reaction”
using 10 mol % of sodium ascorbate and 10 mol %
CuSO4·5H2O as the catalysts.
EXPERIMENTAL
All solvents and reagents of analytical grade were
purchased from Aldrich and SD FineChem. Purity of
products was tested by TLC on silica gel GF254 plates
using UV/Iodine as visualizing agents. Melting points
were measured in open capillaries on an electrical
melting point apparatus and are uncorrected. IR
spectra (KBr) were recorded on a FTIR Perkin–Elmer
1
spectrophotometer. H and 13C NMR spectra were
1501

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APARNA et al.
Scheme 1. Synthesis of bis-1,2,3-triazol-1H-4-yl-substituted aryl benzimidazole-2-thiols 5a–5l.
measured on a Bruker Biospinavance-III (400 MHz)
spectrometer using CDCl3 and DMSO-d6 as solvents
and TMS as an internal reference. Mass spectra were
measured on a MS spectrometer using an ESI mode
positive ion trap detector.
ethyl acetate three times. The combined organic layers
were dried over anhydrous Na2SO4 and the solvent was
evaporated under reduced pressure. The product was
purified by column chromatography to produce pure
compound 3a.
It was determined that the higher yield of 3a was
achieved by using Et3N and DMF as a solvent (Table 2).
Synthesis of propargylated 5-(difluoromethoxy)-
1H-benzimidazole-2-thiol (3a). A mixture of 5-(di-
fluoromethoxy)-1H-benzimidazole-2-thiol 1a
(4.16 mmol) in DMF with 2.3 ml of Et3N was stirred
for 25 min under nitrogen atmosphere, then 2 equiv of
propargyl bromide 2 were added and stirring continued
at room temperature for 10–12 h. After completion of
the process (TLC), the reaction mixture was extracted by
Synthesis of propargylated 5-methoxy-1H-benz-
imidazole-2-thiol (3b). A mixture of 5-methoxy-1H-
benzo[d]imidazole-2-thiol 1b (4.16 mmol) with K2CO3
(12.8 mmol) was stirred for 20 min in DMF at room
temperature under nitrogen atmosphere. To this reaction
mixture, 2 equiv of propargyl bromide 2 (8.33 mmol)
Table 1. Antibacterial activity (MIC) of bis-1,2,3-triazol-1H-4-yl-substituted aryl benzimidazole-2-thiol derivatives 5a–5l
MIC, μg/mL
Compound
Escherichia coli
Salmonella typhi
Pseudomonas aeruginosa
Staphylococcus aureus
Ciprofloxacin
121.41
98.56
–
105.69
95.12
–
158.28
117.25
101.47
–
5a
5b
5c
5d
5e
5f
–
–
–
–
–
–
–
103.56
–
105.67
140.26
68.74
121.08
–
85.63
–
123.57
130.28
58.78
–
–
102.57
5g
5h
129.54
61.78
–
–
5i
5j
5k
5l
96.72
99.04
98.2
93.25
106.78
–
111.27
112.85
106.83
83.47
91.45
98.16
120.68
146.59
118.46
121.67
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SYNTHESIS AND ANTIMICROBIAL ACTIVITY
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Table 2. Optimisation of synthesis of compound 3a catalysed
by CuSO4/Sodium ascorbate
were added drop wise, and the mixture was stirred at room
temperature for 8–10 h.After the completion of the process
(TLC) the reaction mixture was extracted twice by ethyl
acetate, the combined organic layers were washed with
brine, dried over anhydrous Na2SO4, and concentrated
under reduced pressure to afford the compound 3b which
was purified by column chromatography.
Entry
Base
Na2CO3
Na2CO3
NaOH
NaH
Solvent
H2O/PEG
Ethanol
Ethanol
DMSO
DMF
Yield,%
10
1
2
3
4
5
6
25
30
40
45
K2CO3
Et3N
5-(Difluoromethoxy)-1-(prop-2-yn-1-yl)-2-(prop-
2-yn-1-ylthio)-1H-benzimidazole (3a). Yield 80%, mp
160–162°C. 1H NMR spectrum (CDCl3), δ, ppm: 2.83 s
(1H, ≡CH), 2.92 s (1H, ≡CH), 3.72 s (2H, CH2), 4.42 s
(2H, CH2), 6.93 d (1H, J = 7.5Hz, HAr), 7.14 s (1H, HAr),
7.46 s (1H, °CF2H), 7.49 d (1H, J = 7.5Hz, HAr). 13C NMR
spectrum (CDCl3), δ, ppm: 29.7, 30.1, 69.4, 69.7, 72.9,
73.1, 100.9, 104.1, 109.3, 125.2, 139.2, 150.4, 157.1,
165.2. MS: m/z: 293 [M + H]+.
DMF
80
dryness and purified by column chromatography to give
the corresponding pure products 5a–5l.
3-(4-{[(1-{[1-(5-Carboxy-2-methylphenyl)-1H-
1,2,3-triazol-4-yl]methyl}-5-(difluoromethoxy)-1H-
benzo[d]imidazol-2-yl)thio]methyl}-1H-1,2,3-triazol-
1-yl)-4-methylbenzoic acid (5a). Yield 72%, mp
278–280°C. IR spectrum, ν, cm–1: 1558.4 (C=N), 1490.9
1
5-Methoxy-1-(prop-2-yn-1-yl)-2-(prop-2-yn-1-
ylthio)-1H-benzimidazole (3b). Yield 82%, mp 158-
160°C. 1H NMR spectrum (CDCl3), δ, ppm: 2.54 s (1H,
≡CH), 2.82 s (1H, ≡CH), 3.78 s (3H, OCH3), 4.22 s (2H,
CH2), 4.82 s (2H, CH2), 7.36 d (1H, J = 7.5Hz, HAr),
7.54 s (1H, HAr), 7.68 d (1H, J = 7.5Hz, HAr). 13C NMR
spectrum (CDCl3), δ, ppm: 20.4, 21.1, 56.4, 74.5, 74.7,
74.8, 103, 109.2, 119.3, 124.3, 126.5, 130.6, 134.2, 152.4,
161.6. MS: m/z: 257 [M + H]+.
(N=N). H NMR spectrum (DMSO-d6), δ, ppm: 3.2 s
(6H, CH3), 4.2 s (2H, CH2), 6.9-7.8 m (9H, HAr), 7.46 s
(1H, OCF2H), 8.2 s (2H, CH), 10.9 s (2H, COOH). 13C
NMR spectrum (DMSO-d6), δ, ppm: 17.0, 35.0, 48.5,
99.3, 111.7, 113.5, 115.6, 120.2, 126.4, 127.1, 128.0,
133.0, 139.3, 148.4, 151.1, 156.1, 166.0, 167.6; ESI MS:
m/z: 646 [M]+.
3-(4-{[(1-{[1-(3-Carboxyphenyl)-1H-1,2,3-triazol-
4-yl]methyl}-5-(difluoromethoxy)-1H-benzo[d]-
imidazol-2-yl)thio]methyl}-1H-1,2,3-triazol-1-yl)-
benzoic acid (5b). Yield 76%, mp 256–257°C. IR
spectrum, ν, cm–1: 1616 (C=N), 1444 (N=N). 1H NMR
spectrum (DMSO-d6), δ, ppm: 4.88 s (2H, CH2), 5.12 s
(2H, CH2), 7.2 d (1H, J = 7.8 Hz, HAr), 7.32 s (1H, HAr),
7.38s(1H, OCF2H), 7.51d(1H, J=8.2Hz, HAr), 7.9–8.2m
(6H, HAr), 8.9 s (2H, CH), 11.2 s (2H, COOH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 37.2, 47.8, 99.6, 112.2,
114.6, 115.8, 120.4, 126.8, 128.0, 132.6, 136.3, 140.4,
153.4, 156.4, 166.2, 167.2. MS, m/z: 620 [M + 2]+.
Synthesis of azides 4a–4f. Substituted aromatic
amines 14.5 mmol were dissolved in 15 mL of HCl and
15 mL of H2O and maintained at 5°C in ice-salt mixture.
Then a solution of sodium nitrite (21.7 mmol) dissolved
in 10 mL of water was added slowly at 5°C upon stirring.
The following slow addition of sodium azide (21.7 mmol)
dissolved in water (10–12 mL) was proceeding for
30 min at the same temperature. The mixture was stirred
for 5 h.After completion of the reaction (TLC) the product
was extracted by ethyl acetate three times, the combined
organic layers were washed with brine, dried over
anhydrous sodium sulphate, and evaporated to dryness
to yield the corresponding pure substituted azides.
3-(4-{[(1-{[1-(5-Carboxy-2-chlorophenyl)-1H-
1,2,3-triazol-4-yl]methyl}-5-(difluoromethoxy)-1H-
benzo[d]imidazol-2-yl)thio]methyl}-1H-1,2,3-triazol-
1-yl)-4-chlorobenzoic acid (5c). Yield 74%, mp 283–
285°C. IR spectrum, ν, cm–1: 1598 (C=N), 1438(N=N).
1H MR spectrum (DMSO-d6), δ, ppm: 4.86 s (2H, CH2),
5.2 s (2H, CH2), 7.2 d (1H, J = 7.58 Hz), 7.38 s (1H,
OCF2H), 7.62 d ( 1H, J = 7.82 Hz, HAr), 7.72–8.23 m
(7H, HAr), 8.3 s (2H, CH), 11.2 s (2H, COOH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 35.0, 48.5, 103, 111.0,
113.5, 116, 120.2, 127.2, 128.7, 134.3, 139.7, 151.7,
156.1, 166.07, 167.2. MS: m/z: 688 [M + 1]+.
Synthesis of bis-1,2,3-triazol-1H-4-yl-substituted
aryl benzimidazole-2-thiols 5a–5l. To a mixture of
0.34 mmol of 3a or 3b in DMF with 0.68 mmol of an
azide 4a–4f were added solutions of sodium ascorbate
(0.0316 mmol) and CuSO4·5H2O (0.0316 mmol).
The reaction mixture was stirred for 19–20 h at room
temperature. The product obtained was extracted by ethyl
acetate thrice. The combined organic layers were washed
with brine, dried over anhydrous Na2SO4, evaporated to
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APARNA et al.
5-[(Difluoromethoxy)-1-{[1-(2-methoxy-4-
3-(4-{[(1-{[1-(3-Carboxyphenyl)-1H-1,2,3-triazol-
4-yl]methyl}-5-methoxy-1H-benzo[d]imidazol-2-yl)-
thio]methyl}-1H-1,2,3-triazol-1-yl)benzoic acid (5h).
Yield 70%, 278–280°C. IR spectrum, ν, cm–1: 1598
(C=N), 1402 (N=N). 1H NMR spectrum (DMSO-d6), δ,
ppm: 3.89 s (3H, OCH3), 4.58 s (2H, CH2), 5.1 s (2H,
CH2), 7.2 s (1H, HAr), 7.34 d ( 1H, J = 7.61, HAr), 7.52 d
(1H, J = 7.72 Hz, HAr), 7.8–8.12 m (6H, HAr), 8.2 s (2H,
CH), 8.6 s (2H, HAr), 10.9 s ( 2H, COOH). 13C NMR
spectrum (DMSO-d6): 36.2, 49.3, 56.8, 101.3, 111.6,
113.8, 115.8, 119.2, 127.5, 128.6, 130.4, 132.2, 133.6,
134.8, 157.1, 166.5. MS: m/z: 583 [M + H]+.
nitrophenyl)-1H-1,2,3-triazol-4-yl]methyl}-2-{[1-
(2-methoxy-4-nitrophenyl)-1H-1,2,3-triazol-4-yl]-
methyl}thio[-1H-benzimidazole (5d). Yield 75%, mp
275–277°C. IR spectrum, ν, cm–1: 1614 (C=N), 1490
(N=N). 1H NMR spectrum (DMSO-d6), δ, ppm: 3.8 s (6H,
OCH3), 4.2 s (2H, CH2), 4.8 s (2H, CH2), 6.9 d (1H, HAr),
7.24 s (1H, HAr), 7.38 s (1H, OCF2H), 7.48 s (1H, HAr ),
7.8–8.0 m (6H, HAr), 8.2 s (2H, CH). 13C NMR spectrum
(DMSO-d6), δ, ppm: 35.7, 47.4, 56.9, 100.3, 109.2, 111.1,
116.2, 120.7, 123.8, 127.9, 129.1, 132.1, 134.9, 137.6,
140.0, 148.0, 157.6, 158.9, 168.5. MS: m/z: 679 [M – 1]+.
1-{[1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl]-
methyl}-2-{[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]-
methyl}thio-5-(difluoromethoxy)-1H-benzimidazole
(5e). Yield 78%, mp 250–252°C. IR spectrum, ν,
3-(4-{[(1-{[1-(5-Carboxy-2-chlorophenyl)-1H-
1,2,3-triazol-4-yl]methyl}-5-methoxy-1H-benzo[d]-
imidazol-2-yl)thio]methyl}-1H-1,2,3-triazol-1-yl)-4-
chlorobenzoic acid (5i). Yield 75%, mp 290–292°C. IR
spectrum, ν, cm–1: 1597 (C=N), 1436 (N=N). 1H NMR
spectrum (DMSO-d6), δ, ppm: 3.79 s (3H, OCH3), 4.71 s
(2H, CH2), 4.9 s (2H, CH2), 6.9 s (1H, HAr ), 7.34 d (1H,
J = 7.74 Hz, HAr), 7.48 d (1H, J = 7.8 Hz, HAr), 7.5–8.2 m
(8H, HAr), 8.4 s (2H, CH ), 11.2 s (2H, COOH). 13C NMR
spectrum (DMSO-d6): 35.9, 48.5, 54.9, 100.5, 113.5, 116,
125.4, 127.1, 128, 130.9, 131, 133, 137.3, 139.7, 151.1,
156.1, 166. MS: m/z: 652 [M + H]+.
1
cm–1: 1620 (C=N), 1496 (N=N). H NMR spectrum
(DMSO-d6), δ, ppm: 4.8 s (2H, CH2), 5.1 s (2H, CH2),
6.94 d (1H, HAr), 7.18 s (1H, HAr), 7.36 s (1H, OCF2H),
7.46 d (1H, HAr), 7.5-7.8 m (8H, HAr), 8.2 s (2H, CH). 13C
NMR spectrum (DMSO-d6), δ, ppm: 35.4, 49.1, 100.8,
111.7, 115.3, 119.4, 121.7, 122.4, 126.4, 129.8, 132.9,
134.3, 138.9, 152.0, 156.6, 167.6. MS: m/z: 598 [M]+.
4-(4-{[(5-(Difluoromethoxy)-1-{[1-(4-
hydroxyphenyl)-1H-1,2,3-triazol-4-yl]methyl}-
1H-benzo[d]imidazol-2-yl)thio]methyl}-1H-1,2,3-
triazol-1-yl)phenol (5f). Yield 71%, mp 273–275°C. IR
spectrum, ν, cm–1: 1602 (C=N), 1436 (N=N). 1H NMR
spectrum (DMSO-d6), δ, ppm: 4.6 s (2H, CH2), 4.9 s (2H,
CH2), 5.6 s (2H, OH), 7.2 d (1H, HAr), 7.31 s (1H, HAr),
7.38 s (1H, HAr ), 7.5 d (1H, HAr), 7.56 –8.1 m (8H, HAr),
8.2 s (2H, CH). 13C NMR spectrum (DMSO-d6), δ, ppm:
35.3, 47.7, 100.4, 111.5, 113.3, 115.0, 116.5, 119.5, 121.7,
123.9, 125.0, 126.0, 128.4, 132.4, 139.8, 152.0, 156.2,
158.1, 167.5. MS: m/z: 564 [M + 2]+.
5-Methoxy-1-{[1-(2-methoxy-4-nitrophenyl)-
1H-1,2,3-triazol-4-yl]methyl}-2-{[(1-(2-methoxy-4-
nitrophenyl)-1H-1,2,3-triazol-4-yl]methyl]thio}-1H-
benzimidazole (5j). Yield 78%, mp 288–290°C. IR
spectrum, ν, cm–1: 1618 (C=N), 1450 (N=N). 1H NMR
spectrum (DMSO-d6), δ, ppm: 3.9 s (9H, OCH3), 4.8 s
(2H, CH2), 4.9 s (2H, CH2), 7.2 s (1H, HAr), 7.3 d
(1H, J = 7.6 Hz, HAr), 7.45 d (1H, J = 7.8 Hz, HAr),
7.52–8.2 m (6H, HAr), 8.3 s (2H, CH). 13C NMR spectrum
(DMSO-d6): 36.7, 47.9, 57, 100.8, 108.2, 113.7, 118.4,
120.4, 125.1, 130.1, 132.6, 140.6, 142.3, 148, 152.7,
155.9, 158.3. MS: m/z: 645 [M + H]+.
3-(4-{[(1-{[1-(5-Carboxy-2-methylphenyl)-1H-
1,2,3-triazol-4-yl]methyl}-5-methoxy-1H-benzo[d]
imidazol-2-yl)thio]methyl}-1H-1,2,3-triazol-1-yl)-4-
methylbenzoic acid (5g). Yield 73%, mp 286-288°C. IR
spectrum, ν, cm–1: 1622 (C=N), 1435 (N=N). 1H NMR
spectrum (DMSO-d6), δ, ppm: 2.86 s (6H, CH3), 4.1 s
(1H, OCH3), 4.6 s (2H, CH2), 4.9 s (2H, CH2), 6.84 s
(1H, HAr), 7.42 d (1H, HAr), 7.64 d (1H, HAr ), 7.7–8.1 m
(6H, HAr ), 8.3 s (2H, CH), 11.2 s (2H, COOH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 22.0, 42.5, 50.8, 58.2,
100.5, 113.5, 116.0, 120.0, 124.0, 126.0, 128.0, 130.9,
132.2, 133.0, 135.7, 139.7, 144.0, 152.3, 156.1, 166.0.
MS: m/z: 610 [M]+.
1-{[1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl]-
methyl}-2-{[(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-
yl)methyl]thio}-5-methoxy-1H-benzimidazole (5k).
Yield 78%, mp 285–287°C. IR spectrum, ν, cm–1: 1438.9
(C=N), 1313.5 (N=N). 1H NMR spectrum (DMSO-d6),
δ, ppm: 3.82 s (3H, OCH3), 4.8 s (2H, CH2), 4.9 s (2H,
CH2), 7.16 s (1H, HAr), 7.24 d (1H, J = 7.8 Hz, HAr), 7.48 d
(1H, J = 7.9 Hz, HAr), 7.65–8.12 m (8H, HAr), 8.68 s (2H,
CH). 13C NMR spectrum (DMSO-d6): 41.3, 48.1, 57.1,
102.7, 113.1, 114.3, 127.7, 128.9, 133.0, 134.1, 139.4,
153. 9, 157. 2. MS: m/z: 563 [M]+.
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SYNTHESIS AND ANTIMICROBIAL ACTIVITY
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Table 3. Dockscore of imidazole derivatives 5a–5l docked into the active sites of FabI of S. aureus using extra precision (XP)
docking protocol of Glide 5.6
Dockscore,
kcal/mol
–6.091
Not determined
Not determined
Dockscore,
kcal/mol
–3.645
Not determined
–6.192
Dockscore,
kcal/mol
–6.134
–0.942
–6.783
Dockscore,
kcal/mol
–6.211
–6.415
–7.690
Comp. no.
Comp. no.
Comp. no.
Comp. no.
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
4-(4-{[(1-{[1-(4-Hydroxyphenyl)-1H-1,2,3-triazol-
4-yl]methyl}-5-methoxy-1H-benzimidazol-2-yl)thio]
methyl}-1H-1,2,3-triazol-1-yl)phenol (5l). Yield 80%,
mp 258–260°C. IR spectrum, ν, cm–1: 1597 (C=N), 1436
moderate inhibiting activity of enoyl acyl carrier protein
reductase (FabI). The lower dock score and corresponding
low inhibitory activity could be due to bulkiness of the
molecules. Dock pose and molecular interaction diagram
of molecule 5l is shown in Fig. 1. The other major
interactions with the protein were of hydrophobic nature
with amino acid residues Phe 96, Met 99, Tyr147, Tyr157,
and Met 160 (Fig. 2). Molecules of 5l were characterized
by two hydrogen bond interactions with amino acid
residues of Ala 97 and Tyr 157.
1
(N=N). H NMR spectrum (DMSO-d6), δ, ppm: 3.8 s
(3H, OCH3), 4.6 s (2H, CH2), 5.1 s (2H, CH2), 5.5 s (2H,
OH), 6.8–7.5 m (3H, HAr), 7.62–8.1 m (8H, HAr), 8.4 s
13
(2H, CH). C NMR spectrum (DMSO-d6): 42.0, 51.1,
57.4, 100.9, 111, 112, 113, 121.5, 124.2, 125.6, 127.6,
129.2, 133.8, 136.2,153.2,150.1,154.7,159. MS: m/z:
525 [M – H]+.
CONCLUSIONS
Molecular docking studies of compounds 5a–5l.
The synthesized 1,2,3 triazole derivatives were studied
for their molecular docking on high resolution X-ray
crystal structure of FabI of Staphylococcus aureus (pdb id:
4FS3) obtained from protein data bank (http://www.rcsb.
org/) (Table 3). The highest dock score of –7.69 kcal/mol
and the lowest dock score of –0.942 kcal/mol were
obtained for molecule 5l and 5h, respectively. Molecules
of compounds 5b, 5c, and 5e did not dock into the
protein active sites and did not demonstrate inhibitory
activity against the bacterial strains. The molecules of
other products showed moderate dock score, indicating
Novel bis-1,2,3-triazol-1H-4-yl-substituted aryl
benzimidazole-2-thiols 5a–5l have been synthesized from
propargylated benzimidazole-2-thiols and azides using
the “click chemistry.” Antibacterial activity of triazole
derivatives 5a–5l demonstrate moderate to good activity
against gram negative and gram positive bacterial strains.
The products 5i, 5k, and 5l are characterized by a broad
spectrum of antibacterial activity at concentration of
10 μg/mL. The derivative 5l displays the highest dock
score of –7.69 kcal/mol and the least dock score of
–0.942 kcal/mol is obtained for 5h.
Fig. 2. Hydrophobic interactions of molecules of 5l with active
sites of amino acid residues.
Fig. 1. Dock pose of molecule 5l in the active site of FabI.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 8 2020

1506
APARNA et al.
Inard, C., Pasca, M.R., and Baltas, M., Eur. J. Med.
ACKNOWLEDGMENTS
Chem., 2011, vol. 46, no. 11, p. 5524.
https://doi.org/10.1016/j.ejmech.2011.09.013
Authors are grateful to the Head, Department of Chemistry,
Osmania University, Hyderabad for providing laboratory
facilities and also thanks to analytical team, CFRD, Osmania
University and IICT, Hyderabad for providing spectral data.
6. Akselsen, W., Odlo, K., Cheng, J.J., Maccari, G.,
Botta, M., and Hansen, T.V., Bioorg. Med. Chem., 2012,
vol. 20, no. 1, p. 234.
CONFLICT OF INTEREST
https://doi.org/10.1016/j.bmc.2011.11.010
No conflict of interest was declared by the authors.
7. Odlo, K., Hentzen, J., dit Chabert, J.F., Ducki, S.G.,
Sylte, I., Skrede, M., Flørenes, V.A., and Hansen, T.V.,
Bioorg. Med. Chem., 2008, vol. 1, p. 4829.
REFERENCES
https://doi.org/10.1016/j.bmc.2008.03.049.
1. Keri, R.S., Patil, M.R., Patil, S.A., and Budagumpi, S.,
Eur. J. Med. Chem., 2015, vol 89, p. 207.
8. Trond, V.H., Peng, Wu, Sharpless, W.D., and Lind-
berg, J.G., J. Chem. Educ., 2005, vol 82, p. 1833.
https://doi.org/10.1021/ed082p1833
https://doi.org/10.1016/j.ejmech.2014.10.059
2. Bandyopadhyay, P., Sathe, M., Tikar, S.N., Yadav, R.,
Sharma, P., Kumar, A., and Kaushik, M.P., Bioorg.
Med. Chem. Lett., 2014, vol. 24, p. 2934.
9. Jabali, J.V., Trivedi, K.P., and Rahul, S.K., Adv. Appl. Sci.
Res., 2011, vol. 2, p. 89.
https://doi.org/10.1016/j.bmcl.2014.04.082
10. Nandre, R.G. and Mahajan, S.S., Ind. J. Chem., 2006,
vol. 45, p. 1756.
3. Bradshaw, T.D., Chua, M.S., Browne, H.L., Tra-
pani, V, Sausville, E.A., and Stevens, M.F., Br. J. Cancer,
2002, vol. 86, no. 8, p. 1348.
11. Yaowen, L., Chunmei, H., Xinyuan, M., Jianhua, Y.,
Xuepu, F., and Yubo, J., Tetrahedron Lett., 2018, vol. 59,
p. 650.
https://doi.org/10.1038/sj.bjc.6600225
4. Milite, C., Amendola, G., Nocentini, A., Bua, S., Cipri-
ano, A., Barresi, E., Feoli, A., Novellino, E., Da Set-
timo, F., Supuran, C.T., Castellano, S., Cosconati, S.,
and Taliani, S., J. Enzym. Inhib. Med. Chem., 2019,
vol. 34, no. 1, p. 1697.
https://doi.org/10.1016/j.tetlet.2018.01.012
12. Friesner, R.A., Banks, J.L., Murphy, R.B., Halgren, T.A.,
Klicic, J.J., Mainz, D.T., Repasky, M.P., Knoll, E.H.,
Shelley, M., Perry, J.K., Shaw, D.E., Francis, P., and
Shenkin, P.S., J. Med. Chem., 2004, vol. 25, p. 1739.
https://doi.org/10.1021/jm0306430
https://doi.org/10.1080/14756366.2019.1666836
5. Menendez, C., Gau, S., Lherbet, C., Rodriguez, F.,
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