Synthesis, characterization and molecular docking of 1,2,4-triazole derivatives as potential antimicrobial agents

Article abstract of DOI:10.14233/ajchem.2020.22594

In this study, a new series of (E)-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-1-yl)acetamide (32-41) was synthesized, characterized by FT-IR, ¹H NMR, ¹³C NMR and Mass spectral analysis and evaluated for their in

Full text of DOI:10.14233/ajchem.2020.22594

Asian Journal of Chemistry; Vol. 32, No. 6 (2020), 1437-1442
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.22594
Synthesis, Characterization and Molecular Docking of
1,2,4-Triazole Derivatives as Potential Antimicrobial Agents
*
PANNEERSELVAM KALAIVANI, JAYARAMAN ARIKRISHNAN and MANNUTHUSAMY GOPALAKRISHNAN
Department of Chemistry, Annamalai University, Annamalai Nagar, Chidambaram-608002, India
*Corresponding author: E-mail: mgkrishnan61@gmail.com
Received: 16 December 2019;
Accepted: 28 February 2020;
Published online: 30 May 2020;
AJC-19894
In this study, a new series of (E)-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-1-yl)acetamide (32-41) was synthesized,
1
characterized by FT-IR, H NMR, 13C NMR and Mass spectral analysis and evaluated for their in vitro antibacterial and antifungal
activities. The docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site
of 1T9U protein. The zone of inhibition concentration was tested for the synthesized compounds against five bacterial and three fungal
strains. Compounds 34 and 37 have good antibacterial activity. Compounds 3, 4 and 6 shows moderate inhibition against the antifungal activity.
Keywords: 1,2,4-Triazole, Molecular docking, 1T9U Protein, Antibacterial activity, Antifungal activity.
such as antibacterial [9,10], antifungal [11-13], antituberculosis
[14], anticancer [15,16], herbicide [17], anti-inflammatory
[18,19], anticonvulsant [20], antidiabetic [21], antimalarial [22]
and antioxidant [23] activities.Additionally, amide along with
an organic compound as a crucial biologically active group
has higher anticancer, antibacterial and antiviral activities [24-
26]. Besides these, amides are widely recognized for their
therapeutic values. The chemistry of amides having a chloro-
acetyl group became additionally very charming and has received
considerable attention now a day. N-Benzyl-β-chloropropio-
namide a very good anticonvulsant and turned into marketed
below the alternate name Hibicon and Hydrane [27]. Triazole
derivatives are given as fungicides in agrichemicals also as
pharmaceutical applications for the treatment of topical and
systematic fungal infections. The enormous use of triazole
derivatives has generated significant issues regarding their
distribution, free concentration and metabolism among the
body, which is tormented by the ligand-protein interactions
within the bloodstream [28]. In recent years, triazoles have
received unique interest in drug discovery due to many drug
molecules containing triazole groups such as tazobactam,
cephalosporin and cefatrizine [29]. They may be clinically used
for the treatment of microbial infections. Because of these
above findings, it have been contemplated to layout and
synthesize a new magnificence of heterocyclic derivatives
INTRODUCTION
Microbial infections are the maximum distinguished loss
of life-causing disease once an attack within the worldwide,
because of their capacity to unfold quickly, blended with their
toxicity and resistance closer to existing antibiotic drugs [1,2].
Those developments have emphasized the urgent need and
venture for the development of more effective, potent and wide-
spectrum antimicrobial novel drugs with practical bioavail-
ability, no or fewer factor consequences to cure microbial
infections [3]. In this context, drug discovery has obtained a
considerable interest in a microbial target based totally on the
synthesis of novel antimicrobial agents.
Heterocyclic molecules are a reliable source for disco-
vering novel biologically active molecules.Among the hetero-
cyclic compounds, 1,2,4-triazole derivatives represent one of
the most interesting and essential classes of compounds [4].
The nitrogen-based heterocyclic system has been reportable
to procedure numerous pharmacological applications [5].
Triazole that is famous for its effective antimicrobial activity
has won extra involvement in the past many years [6,7]. As a
result of their characteristics together with high biological
activities, excessive efficiency, low toxicity, huge microbial
spectrum and stereoselectivity, etc. [8]. Triazoles are attracting
growing interest in the biological and pharmaceutical fields
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1438 Kalaivani et al.
Asian J. Chem.
in which 1,2,4-triazole derivatives act as an antimicrobial
agent.
δ, ppm: 4.23 (s, 2H, CH2), 7.26 (s, NH), 7.72 (d, CH), 7.57 (d,
CH), 8.06 & 8.5 (s, triazole H). 13C NMR spectrum (CDCl3),
δ, ppm: 188.61 (C=O), 164.08 (amide C=O), 151 (triazole
C3), 141.31, 143.31 (triazole C5), ar C [140.87, 136.49, 134.52,
133.35, 129.2, 122.04, 119.41], 42.90 (CH2). Elemental analysis
for C19H15N4O2Cl (%): C, 62.21; H, 4.12; N, 15.27.
N-(4-(3-(2,3-Dichlorophenyl)acryloyl)phenyl)-2-(1H-
1,2,4-triazol-1-yl)acetamide (34): Yellow solid, yield: 68%,
m.p.: 158-162 °C, m.w.: 401, FT-IR (KBr, νmax, cm–1): 3274
(NH), 3047 (Ar CH), 2927 (Ali CH), 1696 (amide C=O), 1648
(C=O), 1593 (C=N), 1528 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 4.23 (s, 2H, CH2), 7.26 (s, NH), 7.43 (d, CH), 8.15 (d,
CH), 8.04 & 8.48 (s, triazole H). 13C NMR spectrum (CDCl3),
δ, ppm: 188.57 (C=O), 164.1 (amide C=O), 150.85 (triazole
C3), 145.18 (triazole C5), ar C [141, 140.51, 135.63, 133.5,
127.41, 125.92, 119.42], 42.89 (CH2). Elemental analysis for
C19H14N4O2Cl2 (%): C, 56.87; H, 3.52; N, 13.96.
N-(4-(3-(2,6-Dichlorophenyl)acryloyl)phenyl)-2-(1H-
1,2,4-triazol-1-yl)acetamide (35): Yellow solid, yield: 68%,
m.p.: 118-120 °C, m.w.: 401, FT-IR (KBr, νmax, cm–1): 3301
(NH), 3072 (Ar CH), 2930 (Ali CH), 1682 (amide C=O), 1647
(C=O), 1575 (C=N), 1526 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 4.23 (s, 2H, CH2), 7.26 (s, NH), 7.43 (d, CH), 8.15 (d,
CH), 8.04 & 8.48 (s, triazole H). 13C NMR spectrum (CDCl3),
δ, ppm: 188.76 (C=O), 163.87 (amide C=O), 152.81 (triazole
C3), 145.02 (triazole C5), ar C [141.73, 140.51, 137.71, 133.93,
131.42, 129.88, 128.8, 119.1, 113.9], 42.89 (CH2). Elemental
analysis for C19H14N4O2Cl2 (%): C, 56.87; H, 3.52; N, 13.96.
N-(4-(3-(4-Fluorophenyl)acryloyl)phenyl)-2-(1H-1,2,4-
triazol-1-yl)acetamide (36): Yellow solid, yield: 72%, m.p.:
152-156 °C, m.w.: 350, FT-IR (KBr, νmax, cm–1): 3294 (NH),
3050 (Ar CH), 2948 (Ali CH), 1684 (amide C=O), 1660
(C=O), 1593 (C=N), 1532 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 4.23 (s, 2H, CH2), 7.26 (s, NH), 7.7 (d, CH), 7.34 (d,
CH), 8.04 & 8.3 (s, triazole H). 13C NMR spectrum (CDCl3),
δ, ppm: 188.7 (C=O), 165.3 (C=O), 162.85, 151.5 (triazole
C3) 143.53 (triazole C5), ar C [140.77, 134.6, 131.1, 129.9,
121.3, 119.4, 116.06], 42.8 (CH2). Elemental analysis for
C19H15N4O2F (%): C, 65.14; H, 4.32, N, 15.99.
N-(4-(3-(p-Tolyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-
1-yl)acetamide (37):Yellow solid, yield: 76%, m.p.: 172-178
°C, m.w.: 346, FT-IR (KBr, νmax, cm–1): 3310 (NH), 3016 (Ar
CH), 2917 (Ali CH), 1667 (amide C=O), 1655 (C=O), 1597
(C=N), 1538 (C=C). 1H NMR spectrum (CDCl3), δ, ppm: 2.39
(s, CH3), 4.21 (s, 2H, CH2), 7.26 (s, NH), 7.7 (d, CH), 7.34 (d,
CH), 8.03 & 8.5 (s, triazole H). 13C NMR spectrum (CDCl3),
δ, ppm: 189.1 (C=O), 164.14 (amide C=O), 151 (triazole C3),
144.9 (triazole C5), ar C [140.7, 134.8, 132.1, 129.7, 120.64,
119.4], 42.93 (CH2), 21.55 (CH3).Elemental analysis for
C20H18N4O2 (%): C, 69.35; H, 5.24; N, 16.17.
EXPERIMENTAL
Performing TLC assessed the reactions and the purity of
the products. All the reported melting points were taken in
open capillaries and were uncorrected. FT-IR spectra were
recorded in the ATR method on an Agilent Cary 630 FT-IR
spectrophotometer and noteworthy absorption values (cm-1)
were listed. 1H and 13C NMR spectra were recorded at 400 MHz
and 100 MHz, respectively on Brucker Avance II 400 NMR
spectrometer using CDCl3 as a solvent.
General procedure for synthesis of (E)-1-(4-aminophe-
nyl)-3-(3,5-dialkylphenyl)prop-2-en-1-ones (12-21): The
Claisen-Schmidt condensation reaction of equimolar quantities
of aminoacetophenone (1, 0.01 mol) and substituted benzal-
dehyde (2-11, 0.01 mol) were stirred at room temperature in
an ethanolic solution of potassium hydroxide for 2-3 h. The
formed yellow crystals were filtered off, washed with distilled
water, dried and recrystallized from ethanol.
General procedure for synthesis of (E)-2-chloro-N-(4-
(3-(3,5-dialkylphenyl)acryloyl)phenyl)acetamide (22-31):
The electrophilic substitution reaction of chloroacetyl chloride
(0.01 mol) with the corresponding parent (E)-1-(4-aminophenyl)-
3-(3,5-dialkylphenyl)prop-2-en-1-ones (12-21, 0.01 mol) in
the presence of triethylamine as a base and dichloromethane
(20 mL) as a solvent, was stirred at room temperature. The
reaction process was monitored by TLC.After the completion,
the reaction mixture was extracted with chloroform. The organic
layer was separated and dried over-under vacuum. The crude
product was collected and purified.
General procedure for synthesis of (E)-N-(4-(3-(3,5-
dialkylphenyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-1-
yl)acetamide (32-41):A mixture of (E)-2-chloro-N-(4-(3-(3,5-
dialkylphenyl)acryloyl)phenyl)acetamide (22-31) (0.05 mol),
potassium carbonate (0.01 mol) and 1,2,4-triazole (0.05 mmol)
in dimethylformamide was refluxed. After completion of the
reaction was monitored by TLC. The reaction was poured into
ice-cold water. The product was washed and filtered with water
and then recrystallized from ethanol.
Physical properties and spectral data
N-(4-(3-(3-chlorophenyl)acryloyl)phenyl)-2-(1H-1,2,4-
triazol-1-yl)acetamide (32): Yellow solid, yield: 72%, m.p.:
112-114 °C, m.w.: 366, FT-IR (KBr, νmax, cm–1): 3314 (NH),
3050 (Ar CH), 2925 (Ali CH), 1684 (amide C=O), 1660
(C=O), 1595 (C=N), 1530 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 4.24 (s, 2H, CH2), 7.26 (s, NH), 7.75 (d, CH), 7.59 (d,
CH), 8.05 & 8.6 (s, triazole H). 13C NMR spectrum (CDCl3),
δ, ppm: 188.7 (C=O), 161.9 (amide C=O), 151 (triazole C3),
141.8, 143.3 (triazole C5), ar C [140.8, 134.9, 130.2, 127.9, 126.8,
122.9, 119.4], 42.9 (CH2). Elemental analysis for C19H15N4O2Cl
(%): C, 62.21; H, 4.12; N, 15.27.
N-(4-(3-(4-Chlorophenyl)acryloyl)phenyl)-2-(1H-
1,2,4-triazol-1-yl)acetamide (33): Yellow solid, yield: 70%,
m.p.: 174-180 °C, m.w.: 366, FT-IR (KBr, νmax, cm–1): 3309
(NH), 3057 (Ar CH), 2953 (Ali CH), 1697 (amide C=O), 1655
(C=O), 1597 (C=N), 1529 (C=C). 1H NMR spectrum (CDCl3),
N-(4-(3-(3-Methoxyphenyl)acryloyl)phenyl)-2-(1H-
1,2,4-triazol-1-yl)acetamide (38): Yellow solid, yield: 78%,
m.p.: 128-132 °C, m.w.: 362, FT-IR (KBr, νmax, cm–1): 3282
(NH), 3053 (Ar CH), 2939 (Ali CH), 1697 (amide C=O), 1655
(C=O), 1593 (C=N), 1525 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 3.85 (s, 3H, OCH3), 4.29 (s, 2H, CH2), 7.26 (s, NH),
7.7 (d, CH), 7.3 (d, CH), 8.03 & 8.56 (s, triazole H). 13C NMR
spectrum (CDCl3), δ, ppm: 188.97 (C=O), 164.15 (amide C=O),

Vol. 32, No. 6 (2020)
Synthesis and Molecular Docking of 1,2,4-Triazole Derivatives as Potential Antimicrobial Agents 1439
159.94, 151 (triazole C3), 144.76 (triazole C5), ar C [140.84,
136.2, 134.61, 129.96, 121.95, 119.4], 55.37 (OCH3), 42.94
(CH2). Elemental analysis for C20H18N4O3 (%): C, 66.29; H,
5.01; N, 15.46.
amino acid residues. The interaction of the ligand molecule
with the 1T9U protein and ligand poses have been analyzed
and studied based on H-bonding poses to the receptor molecule
and vander Waals interaction between the poses and receptor
molecule. The unwanted water molecules, chains and co-factors
were removed.
Antimicrobial activity: The in vitro antimicrobial activity
was carried out by disc diffusion method [32,33]. The newly
synthesized compounds were evaluated for their antibacterial
activity towards a panel of pathogenic microorganisms, which
includes three Gram-positive bacterial strains Bacillus subtilis,
Staphylococcus aureus, Proteus vulgaris and two Gram-negative
bacterial strains Escherichia coli, Pseudomonas aeroginosa.
On the other hand, Candida albicans, Candida parapsilosis
and Candida tropicalis had been chosen to study the antifungal
activities of the synthesized compounds. The antibacterial and
antifungal screening revealed that some of the examined com-
pounds demonstrated fair to good antimicrobial activities
relative to ciprofloxacin and fluconazole; standard potent anti-
bacterial and antifungal, respectively.
The bacterial and fungal strains have been chosen based
totally on their medical and pharmacological importance.
Nutrient agar plates were prepared aseptically to get a thickness
of 5-6 mm. The plates had been allowed to solidify and inverted
to prevent condensate from falling on the agar surface. The
plates were dried at 37 °C just before inoculation. The sterilized
discs for the test drugs were placed in the petri dish at 37 0.2
°C for about 18-24 h; after placing them in the refrigerator for
1 h to facilitate uniform diffusion. The average zone diameter
of the plates was measured and recorded. All the synthesized
compounds were tested for antibacterial and antifungal acti-
vities against the bacterial and fungal strains.
N-(4-(3-(4-Methoxyphenyl)acryloyl)phenyl)-2-(1H-
1,2,4-triazol-1-yl)acetamide (39): Yellow solid, yield: 78%,
m.p.: 142-146 °C, m.w.: 362, FT-IR (KBr, νmax, cm–1): 3260
(NH), 3055 (Ar CH), 2929 (Ali CH), 1683 (amide C=O), 1654
(C=O), 1594 (C=N), 1529 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 3.85 (s, 3H, OCH3), 4.2 (s, 2H, CH2), 7.26 (s, NH),
7.7 (d, CH), 7.3 (d, CH), 8.03 & 8.5 (s, triazole H). 13C NMR
spectrum (CDCl3), δ, ppm: 189.03 (C=O), 164.09 (amide C=O),
161.74, 151 (triazole C3), 144.75 (triazole C5), ar C [140.58,
134.98, 131.61, 129.85, 127.5, 119.3], 55.43 (OCH3), 42.91
(CH2). Elemental analysis for C20H18N4O3 (%): C, 66.29; H,
5.01; N, 15.46.
N-(4-(3-(3,5-Dimethoxyphenyl)acryloyl)phenyl)-2-
(1H-1,2,4-triazol-1-yl)acetamide (40): Yellow solid, yield:
76%, m.p.: 162-166 °C, m.w.: 392, FT-IR (KBr, νmax, cm–1):
3255 (NH), 3097 (Ar CH), 2940 (Ali CH), 1683 (amide C=O),
1
1655 (C=O), 1589 (C=N), 1535 (C=C). H NMR spectrum
(CDCl3), δ, ppm: 3.74 (s, 6H, OCH3), 4.2 (s, 2H, CH2), 7.26
(s, NH), 7.7 (d, CH), 7.4 (d, CH), 8.06 & 8.2 (s, triazole H).
13C NMR spectrum (CDCl3), δ, ppm: 189.3 (C=O), 164.09
(amide C=O), 161.05, 151 (triazole C3), 145 (triazole C5), ar
C [140.7, 134.8, 132.1, 129.9, 122.1, 119.48], 55.48 (OCH3),
42.93 (CH2). Elemental analysis for C21H20N4O4 (%): C, 64.28;
H, 5.14; N, 14.28.
N-(4-(3-(3-Nitrophenyl)acryloyl)phenyl)-2-(1H-1,2,4-
triazol-1-yl)acetamide (41): Yellow solid, yield: 56%, m.p.:
138-142 °C, m.w.: 377, FT-IR (KBr, νmax, cm–1): 3261 (NH),
3090 (Ar CH), 2916 (Ali CH), 1667 (amide C=O), 1656
(C=O), 1594 (C=N), 1519 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 4.24 (s, 2H, CH2), 7.26 (s, NH), 7.7 (d, CH), 7.64 (d,
CH), 8.08 & 8.52 (s, triazole H). 13C NMR spectrum (CDCl3),
δ, ppm: 188.04 (C=O), 164.11 (amide C=O), 152.02 (triazole
C3), 145.18 (triazole C5), ar C [141.64, 136.6, 134.09, 130.12,
124.28, 120, 119.5], 42.9 (CH2).Elemental analysis for
C19H15N5O4 (%): C, 60.47; H, 4.01; N, 18.56.
Molecular docking study: Molecular docking study is
to predict the binding orientation of ligands to their protein
and in turn expecting the binding affinity and strength of
affiliation among the target and ligand. Molecular docking
was completed among the active binding area of the energy
minimized to stabilize the structure of 1T9U and the synthe-
sized compounds the use of the CDOCKER docking protocol
of the Discovery studio. CDOCKER is a grid-based molecular
dynamic algorithm that employs the CHARMm force field
using the ligand minimization tool [30].
Molecular docking studies were finished through by Bio-
via discovery studio, 2016 software become utilized in perfor-
ming this docking simulation study. The X-ray 3D crystal struc-
ture of bacterial multidrug efflux transporter AcrB (PDB ID:
1T9U) was retrieved from protein data bank with a good reso-
lution of 3.5 Å [31].After the docking process, the CDOCKER
energy and CDOCKER interaction energy scores have been
displayed within the output file. The best ligand was chosen,
based on their lowest interaction energy and highly interacting
RESULTS AND DISCUSSION
A three-step synthetic route furnished the target compo-
unds in good yields. General schematic representations are
given in Scheme-I. The Claisen-Schmidt condensation reaction
of equimolar quantities of 4-amino acetophenone and appro-
priate benzaldehyde in the presence of alcoholic KOH yielded
(E)-1-(4-aminophenyl)-3-(3,5-dialkylphenyl)prop-2-en-1-
ones (12-21). Then, various substituted (E)-2-chloro-N-(4-(3-
(3,5-dialkylphenyl)acryloyl)phenyl)acetamide (22-31) were
synthesized by the electrophilic substitution reaction of chloro-
acetyl chloride with the corresponding parent (E)-1-(4-amino-
phenyl)-3-(3,5-dialkylphenyl)prop-2-en-1-ones (12-21) in the
presence of triethylamine as a base and dichloromethane as
solvent, appreciable yields were obtained. Then condensation
of (E)-2-chloro-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-
acetamide (22-31)with 1,2,4-triazole in the presence of potassium
carbonate in DMF furnished (E)-N-(4-(3-(3,5-dialkyl-phenyl)-
acryloyl)phenyl)-2-(1H-1,2,4-triazol-1-yl)acetamide (32-41).
The help of the melting points, elemental analysis, FT-IR, one-
dimensional NMR (1H and 13C) and mass spectra supported
the structures of all the newly synthesized compounds. In the
FT-IR spectra of the targeted compounds 32-41 contained a
stretching absorption peak at 3310-3250 assigned due to N-H
stretch. The absorption peak for C=N was observed at 1593

1440 Kalaivani et al.
Asian J. Chem.
H3C
O
H
O
H2N
KOH, EtOH
Stirring
+
R
R
O
NH2
(1)
(
)-1-(4-aminophenyl)-3-(3,5-dialkylphenyl)prop-2-en-1-one
E
(2-11)
(12-21)
Et3N
O
Cl
Cl
Stirring
H
N
H
N
1,2,4-Triazole
N
N
Cl
R
K2CO3, DMF
reflux
R
O
N
O
O
O
(E)-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-1-yl)acetamide
(E)-2-chloro-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)acetamide
(32-41)
(22-31)
Compd
38
39
36
40
41
35
37
33
34
32
2,3-diCl 2,6-diCl
4-CH3
3,5-diOCH3
3-Cl
4-Cl
4-F
3-OCH3 4-OCH3
4-NO2
R
Scheme-I: Synthesis of (E)-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-1-yl)acetamide
cm-1. The peak at 1680 and 1655 cm-1 was assigned due to
TABLE-1
amide C=O and chalcone C=O stretch, respectively. In the1H
DOCKING RESULTS OF THE DESIGNED
COMPOUNDS 32-41 TOWARDS 1T9U
NMR spectrum showed two singlets at δ (ppm) 8.0 and 8.5
-CDOCKER energy
(kcal/mol)
-CDOCKER interaction
energy (kcal/mol)
were assigned to CH protons of the 1,2,4-triazole ring, the
singlet signal at δ 7.26 was assigned to NH proton. The singlet
appeared at δ 4.2 due to CH2 proton, the two doublet signal at
δ 7.4 and 7.7 integrating for two protons were assigned for two
olefin protons (CH=CH). In the 13C NMR spectrum showed
signals at δ (ppm) 188 and 164 corresponds to chalcone and
amide carbonyl carbons, the signals at δ 151 and 144 represents
C3 and C5 carbons of triazole ring, respectively.
Compounds
4.297
3.01
30.957
33.898
30.991
31.446
27.624
30.06
30.743
30.531
34.663
31.772
32
33
34
35
36
37
38
39
40
41
11.535
6.631
7.858
3.923
6.017
6.148
5.522
6.818
Molecular docking studies: The synthesized compounds
32-41 were docked with 1T9U protein. The data obtained from
the docking study is presented in Table-1. The docking results
indicated the active pocket by forming hydrophobic inter-
actions with amino acid residues. The compound 34 had shown
hydrogen-bonding interaction with amino acid residues,
respectively (Fig. 1). The halogen-substituted compounds 34,
35 and 36 were more favourable for hydrophobic interactions
as compared to the other substituted (NO2, OCH3, CH3) com-
pounds. The 4-F substitution in the benzyl ring of most active
compound 36 fitted well into the hydrophobic pocket. The
binding interactions for compound 34 are shown in Fig. 2.
(a)
(b)
Interactions
Conventional hydrogen bond
Pi-Pi T-shaped
Pi-Alkyl
Carbon hydrogen bond
Pi-Donor hydrogen bond
Fig. 1. 2D (a) and 3D (b) model of compound 34 docked with 1T9U protein

Vol. 32, No. 6 (2020)
Synthesis and Molecular Docking of 1,2,4-Triazole Derivatives as Potential Antimicrobial Agents 1441
bacterial strains. Compounds 39 show better activity against
the all bacterial strains, respectively.
Antifungal activity: The in vitro antifungal activity of
(E)-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-2-(1H-1,2,4-
triazol-1-yl)acetamide (32-41) was studied against the fungal
strains Candida albicans, Candida tropicalis, Candida para-
psilosis. Fluconazole was used as a standard drug. The zone
of inhibition was reproduced in Table-2. Compounds 35, 36
and 37 did not exhibit antifungal activity against Candida
tropicalis and Candida parapsilosis. Further introduction of
electron-withdrawing Cl functional group of the phenyl ring
in compounds 32, 33 and 34 better activity against Candida
albicans and Candida tropicalis. Instead of Cl group attached
at ortho and meta position of the phenyl ring in compound 34
exhibits excellent activity against the Candida parapsilosis.
Compounds 38, 39 and 40, which contain electron-donating
methoxy functional group, attached to the phenyl ring exhibits
better activity against Candida tropicalis and Candida
Fig. 2. Docking interactions of 1T9U protein with compound 34
parapsilosis. Also, compound 41 which contains nitro group
at the para position shows potent activity against Candida
albicans and Candida tropicalis.
Antibacterial activity: Novel (E)-N-(4-(3-(3,5-dialkyl-
phenyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-1-yl)acetamide
(32-41) were tested for their antibacterial activity against
Staphylococcus aureus, Bacillus subtilis, Escherichia coli,
Proteus vulgaris and Pseudomonas aeruginosa. Ciprofloxacin
was used as a standard drug. The zone of inhibition values
are shown in Table-2. Of the ten compounds, 32-41 tested for
their antibacterial activity by the disc diffusion method.
Compounds 38, 39 and 40, which have an electron-donating
methoxy group attached to the phenyl ring exhibits moderate
activity. The introduction of para fluoro substituted phenyl
ring was found to enhance the antibacterial activity potency
significantly. Thus, the compounds 33 and 34, which have
electron-withdrawing Cl, group attached to the phenyl ring
exhibits excellent antibacterial activity against Bacillus subtilis
and E. coli. Compounds 32 having a Cl group in the meta
position shows better activity against Staphylococcus aureus
and E. coli. Compound 35 did not promote activity against E.
coli and Proteus vulgaris. The introduction of the nitro group
was found to enhance the potency significantly. Whereas
compounds 37, which have methyl group at the para position
of the phenyl ring did not have high activity against the all
Conclusion
A three step synthetic route was furnished the target com-
pounds (E)-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-2-
(1H-1,2,4-triazol-1-yl)acetamide (32-41) in good yields. The
compounds were characterized by their physical and analytical
data. The docking research of synthesized compounds with
1T9U protein confirmed specific binding interactions and formed
various hydrophobic interactions with active site residues. The
in vitro antimicrobiological studies had been assess the anti-
bacterial and antifungal potencies of the newly synthesized
compounds.A close inspection of the diverse electron-donating
(–CH3, –OCH3) and electron-withdrawing (–F, –Cl) functional
group substituted in the phenyl ring of target compounds
exerted good antibacterial and antifungal activities against the
all bacterial and fungal species.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests
regarding the publication of this article.
TABLE-2
ANTIBACTERIAL AND ANTIFUNGAL ACTIVITIES OF SYNTHESIZED COMPOUNDS 32-41 BY DISC DIFFUSION METHOD
Zone of inhibition (mm)
Antibacterial activity
Staphylococcus Escherichia
Antifungal activity
Candida
Compounds
Bacillus
subtilis
19
Pseudomonas
aeruginosa
23
Proteus
vulgaris
–
18
21
-
20
20
20
20
20
18
26
–
Candida
albicans
12
Candida
tropicalis
10
aureus
23
23
20
19
21
18
22
22
23
18
28
–
coli
20
26
21
–
18
18
24
19
21
22
28
–
parapsilosis
12
32
33
34
35
36
37
38
39
40
18
16
10
14
11
16
12
12
16
10
13
–
10
–
11
10
09
10
–
14
16
14
14
–
10
12
10
15
14
28
23
18
21
18
19
18
24
20
32
–
23
22
20
18
21
22
22
21
21
24
–
41
Ciprofloxacin
Fluconazole
–
20
–
19

1442 Kalaivani et al.
Asian J. Chem.
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