Synthesis and microbicidal activity of substituted 1,2,3-triazoles having amide and hydroxy functionality

Article abstract of DOI:10.14233/ajchem.2017.20660

A series of 1,4-disubstituted 1,2,3-triazoles was designed and synthesized from hydroxy terminal alkynes and 2-azido-N-substituted Nphenylpropanamides. All the synthesized substituted triazoles were characterized by spectral techniques (FT-IR, 1H NMR, 13C

Full text of DOI:10.14233/ajchem.2017.20660

Asian Journal of Chemistry; Vol. 29, No. 10 (2017), 2149-2153
ASIAN JOURNAL OF CHEMISTRY
https://doi.org/10.14233/ajchem.2017.20660
Synthesis and Microbicidal Activity of Substituted
1,2,3-Triazoles having Amide and Hydroxy Functionality
*
C.P. KAUSHIK and RAJ LUXMI
Department of Chemistry, Guru Jambheshwar University of Science & Technology, Hisar-125 001, India
*Corresponding author: Fax: +91 1662 276240; Tel: +91 1662 263152; E-mail: kaushikcp@gmail.com
Received: 20 March 2017;
Accepted: 31 May 2017;
Published online: 31 August 2017;
AJC-18509
A series of 1,4-disubstituted 1,2,3-triazoles was designed and synthesized from hydroxy terminal alkynes and 2-azido-N-substituted N-
1
phenylpropanamides. All the synthesized substituted triazoles were characterized by spectral techniques (FT-IR, H NMR, 13C NMR,
HRMS) and explored for in vitro antimicrobial activity against three Gram-negative bacteria Escherichia coli, Enterobacter aerogenes,
Klebsiella pneumoniae; one Gram-positive bacteria Staphylococcus aureus and two fungal strains Candida albicans and Aspergillus
niger. The bioactive assay of synthesized triazoles reflected moderate to good antibacterial and antifungal efficacy.
Keywords: Click chemistry, Substituted 1,2,3-triazoles, Microbicidal activity.
Here, we sought to synthesize 1,4-disubstituted 1,2,3-
triazoles having amide and hydroxy functionality from the
reaction of terminal alkynes and 2-azido-N-substituted N-
phenylpropanamides (generated in situ from reaction of 2-
bromo-N-substituted-N-phenylpropanamides and sodium
azide). The synthesized triazoles were characterized by various
INTRODUCTION
An antimicrobial is an agent that kills microorganisms or
inhibits their growth. The search for new molecules with broad
spectrum of antimicrobial properties is challenging task to
researchers. In view of continuous enhancement of microbial
infection in society, the triazole ring system possess appreciable
biocompatibility and can play a pivotal role in designing new
potent antimicrobials. Triazole moieties are found to show
antimalarial [1,2], antioxidant [3], antitrypanosomal [4], anti-
inflammatory [5,6], antibacterial [7-9], antifungal [10-12],
antiproliferative [13], antiprotozoal [14], antituberculosis
[15,16] and anticancer [17,18]. Further, 1,4-disubstituted 1,2,3-
triazoles serve as effective bioactive molecule being stable to
reaction conditions i.e., oxidation, reduction, hydrolysis and
participate in hydrogen bonding with biological system.
The dipolar [3+2] cycloaddition of organic azides and
terminal alkynes is the usual method for the synthesis of 1,2,3-
triazoles. This reaction was comprehensively studied by
Huisgen and Padwa [19] yielding 1,4 and 1,5-disubstituted
1,2,3-triazoles variant of substituted 1,2,3-triazole. Later,
Sharpless et al. [20] and Meldal [21] developed Cu(I) catalyzed
azide-alkyne cycloaddition (CuAAC) through “Click
Chemistry” concept results into formation of 1,4-disubstituted
1,2,3-triazoles.The “Click Chemistry” projected cycloaddition
reactions are prime important due to its several advantages in
form of regioselectivity, wide substrate scope, mild reaction
conditions and excellent yields.
1
spectroscopic techniques viz., FT-IR, H NMR, 13C NMR,
HRMS and evaluated for microbicidal activity against Escherichia
coli, Enterobacter aerogenes, Klebsiella pneumoniae, Staphylo-
coccus aureus, Candida albicans and Aspergillus niger.
EXPERIMENTAL
All the chemicals and solvents were purchased from
Sigma-Aldrich, AlfaAesar and Hi-Media. The reactions were
monitored by thin layer chromatography using n-hexane, ethyl
acetate and chloroform in different ratios as mobile phase.
The melting points of synthesized compounds were recorded in
°C by applying an open capillary method and are uncorrected.
1H NMR and 13C NMR spectra were recorded on a Bruker
Avance II 400 MHz at 400 MHz and 100 MHz, respectively,
using DMSO as solvents. Chemical shift values are recorded
on δ scale and the coupling constants (J) in Hertz. HRMS
were obtained using a Waters Micromass Q-T of Micro (ESI)
spectrophotometer and values were recorded in m/z. The IR
spectra were recorded on Shimadzu IR affinity-I FTIR spectro-
photometer using KBr powder.
General procedure for the synthesis of 1,4-disubstituted
1,2,3-triazoles: A solution of aromatic amines (1a-1c) (1.0

2150 Kaushik et al.
Asian J. Chem.
mmol) in dichloromethane was taken in round bottom flask
with potassium carbonate (1.5 mmol) as base and drop-wise
addition of 2-bromopropanoyl bromide (1.2 mmol) was carried
out at 0-5 °C and strirred the contents for 15-20 min. After the
completion of reaction, ice cold water was added to the reaction
mixture, the resulting solid, 2-bromo-N-substituted N-phenyl-
propanamide (3a-3c) was filtered and dried.
84 %; m.p. 130-134 °C; IR (KBr, νmax, cm-1): 3380 (O-H str.),
3148 (C-H str. triazole), 3064 (C-H str. aromatic ring), 2980
(C-H str., aliphatic), 1663 (C=O str. amide), 1542, 1463 (C=C
1
str., aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.81
(s, 1H, C-H triazole), 7.53-7.38 (m, 5H, Ar-H), 5.47 (q, 1H, J
= 7.2 Hz), 5.10 (s, 1H, OH), 2.95 (s, 3H), 1.54 (d, 3H, J = 7.2
Hz), 1.48 (s, 6H): 13C NMR (100 MHz, DMSO-d6): δ 168.4
(C=O), 155.9 (C4 triazole), 142.8, 130.8, 128.8, 127.8, 119.7
(C5 triazole), 67.8, 55.3, 38.0, 31.1, 18.5; HRMS (m/z) calcu-
lated for C16H20N4O2 [M+H]+: 289.1586. Found: 289.1661.
N-Ethyl-2-[4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-
1-yl]-N-phenylpropanamide (5e): White solid;Yield: 85 %;
m.p. 142-144 °C; IR (KBr, νmax, cm-1): 3384 (O-H str.), 3140
(C-H str. triazole), 3070 (C-H str. aromatic ring), 2980 (C-H
str., aliphatic), 1658 (C=O str. amide), 1543, 1463 (C=C str.,
For the synthesis of target compounds 5a-5i, the starting
reactant 2-bromo-N-substituted propanamide (3a-3c) was
stirred with aqueous sodium azide (3.0 mmol) in dimethyl
formamide for 30 min at 35-50 °C in round bottom flask. In
above mixture terminal hydroxyalkyne (4a-4c), aqueous
CuSO4·5H2O (0.1 mmol) and sodium ascorbate (0.4 mmol)
were added and stirring was continued for 8-10 h at same
temperature. After the completion of reaction, ice cold water
was added to the reaction mixture, then filtered the precipitated
solid, washed with aqueous ammonia solution followed by
water. The solid product was recrystallized with ethyl acetate
to get pure product (5a-5i).
1
aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.80 (s,
1H, C-H triazole), 7.53-7.38 (m, 5H, Ar-H), 5.27 (q, 1H, J = 8
Hz), 5.08 (s, 1H, OH), 3.19 (q, 2H, J = 8 Hz), 1.54 (d, 3H, J =
8 Hz), 1.48 (s, 6H), 1.01 (t, 3H, J = 8 Hz); 13C NMR (100 MHz,
DMSO-d6): δ 168.4 (C=O), 155.9 (C4 triazole), 142.8, 130.5,
128.8, 127.8, 119.9 (C5 triazole), 67.5, 55.3, 38.0, 31.1, 18.5,
12.9; HRMS (m/z) calculated for C16H22N4O2 [M+H]+:
303.1403. Found: 303.1461.
2-[4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl]-N-methyl-
N-phenylpropanamide (5a): White solid; Yield: 86 %; m.p.
94-96 °C; IR (KBr, νmax, cm-1): 3380 (O-H str.), 3140 (C-H str.
triazole), 3058 (C-H str. aromatic ring), 2954 (C-H str.,
aliphatic), 1662 (C=O str. amide), 1554, 1454 (C=C str.,
2-[4-(2-Hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl]-
N,N-diphenylpropanamide (5f): White solid; Yield: 78 %;
m.p. 116-118 °C; IR (KBr, νmax, cm-1): 3390 (O-H str.), 3163
(C-H str. triazole), 3043 (C-H str. aromatic ring), 2978 (C-H
str., aliphatic), 1676 (C=O str. amide), 1593, 1452 (C=C str.,
aromatic ring); 1H NMR (400 MHz, DMSO-d6): δ 7.80 (s,
1H, C-H triazole), 7.43 (brs, 10H, Ar-H), 5.47 (q, 1H, J = 7.2
Hz), 5.09 (s, 1H), 1.65 (d, 3H, J = 7.2 Hz), 1.47 (s, 6H); 13C
NMR (100 MHz, DMSO-d6): δ 168.8 (C=O), 156.0 (C4
triazole), 128.8, 127.3, 120.1 (C5 triazole), 67.5, 56.2, 31.3,
18.5; HRMS (m/z) calculated for C20H22N4O2[M+H]+:
351.1743. Found: 351.1813.
1
aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.96 (s,
1H, C-H triazole), 7.56-7.33 (m, 5H, Ar-H), 5.53 (q, 1H, J =
7.2 Hz), 5.22 (s, 1H), 4.55 (s, 2H, OCH2, J = 8 Hz), 2.95 (s,
3H), 1.54 (d, 3H, J = 7.2 Hz); 13C NMR (100 MHz, DMSO-
d6): δ 168.0 (C=O), 148.1 (C4 triazole), 141.0, 130.5, 129.0,
128.9, 122.3 (C5 triazole), 55.7, 55.5, 38.3, 18.0; HRMS (m/z)
calculated for C14H16N4O2 [M+H]+: 261.1273. Found: 261.1343.
N-Ethyl-2-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-
N-phenylpropanamide (5b): White solid; Yield: 86 %; m.p.
76-78 °C; IR (KBr, νmax, cm-1): 3378 (O-H str.), 3142 (C-H str.
triazole), 3058 (C-H str. aromatic ring), 2954 (C-H str.,
aliphatic), 1666 (C=O str. amide), 1554, 1510, 1454 (C=C
2-[4-(2-Hydroxybutan-2-yl)-1H-1,2,3-triazol-1-yl]-N-
methyl-N-phenylpropanamide (5g): White solid; Yield: 90
%; m.p. 66-68 °C; IR (KBr, νm-ax, cm-1): 3378 (O-H str.), 3140
(C-H str. triazole), 3057 (C-H str. aromatic ring), 2978 (C-H
str., aliphatic), 1665 (C=O str. amide), 1593, 1454 (C=C str.,
1
str., aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.95
(s, 1H, C-H triazole), 7.56-7.33 (m, 5H, Ar-H), 5.23-5.16 (m,
2H), 4.49 (d, 2H, OCH2, J = 8 Hz), 3.70 (q, 2H, J = 6.4 Hz),
1.54 (d, 3H, J = 8 Hz), 1.02 (t, 3H, J = 6.4 Hz); 13C NMR (100
MHz, DMSO-d6): δ 168.0 (C=O), 148.1 (C4 triazole), 141.0,
130.5, 129.0, 128.8, 122.3 (C5 triazole), 55.7, 55.5, 44.6, 18.3,
12.9; HRMS (m/z) calculated for C14H18N4O2 [M+H]+:
275.1430. Found: 275.1503.
1
aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.77 (s,
1H, C-H triazole), 7.52-7.34 (m, 5H, Ar-H), 5.47 (q, 1H, J =
6.8 Hz), 5.10 (s, 1H, OH), 2.95 (s, 3H), 1.71 (t, 2H, J = 7.6
Hz), 1.54-1.40 (m, 6H), 0.74 (t, 3H, J = 7.6 Hz); 13C NMR
(100 MHz, DMSO-d6): δ 167.9 (C=O), 155.0 (C4 triazole),
141.0, 130.5, 129.0, 128.8, 120.6 (C5 triazole), 70.2, 55.6, 44.5,
37.6, 35.9, 28.6, 18.1, 8.8; HRMS (m/z) calculated for
C17H22N4O2 [M+H]+: 303.1743. Found: 303.1874.
2-[4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl]-N,N-
diphenylpropanamide (5c): White solid; Yield: 93 %; m.p.
152-154 °C; IR (KBr, νmax, cm-1): 3383 (O-H str.), 3172 (C-H
str. triazole), 3061 (C-H str. aromatic ring), 2968 (C-H str.,
aliphatic), 1676 (C=O str. amide), 1593, 1454 (C=C str.,
N-Ethyl-2-[4-(2-hydroxybutan-2-yl)-1H-1,2,3-triazol-
1-yl]-N-phenylpropanamide (5h): White solid;Yield: 90 %;
m.p. 68-70 °C; IR (KBr, νm-ax, cm-1): 3380 (O-H str.), 3140
(C-H str. triazole), 3057 (C-H str. aromatic ring), 2978 (C-H
str., aliphatic), 1662 (C=O str. amide), 1593, 1454 (C=C str.,
1
aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.97 (s,
1H, C-H triazole), 7.42 (brs, 10H, Ar-H), 5.48 (q, 1H, J = 7.2
Hz), 5.19 (t, 1H, J = 5.6 Hz), 4.51 (d, 2H, OCH2, J = 5.6 Hz),
1.67 (d, 3H, J = 7.2 Hz); 13C NMR (100 MHz, DMSO-d6): δ
168.9 (C=O), 148.2 (C4 triazole), 130.7, 129.6, 129.1, 127.3,
122.4 (C5 triazole), 56.2, 55.5, 18.3; HRMS (m/z) calcu-lated
for C18H18N4O2 [M+H]+: 323.1430. Found: 323.1501.
1
aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.76 (s,
1H, C-H triazole), 7.51-7.34 (m, 5H, Ar-H), 5.19 (q, 1H, J =
6.8 Hz), 4.93 (s, 1H, OH), 3.67 (q, 2H, J = 6.4 Hz), 1.73-1.40
(m, 6H), 1.01 (t, 3H, J = 6.4 Hz), 0.74 (t, 3H, J = 8 Hz); 13C
NMR (100 MHz, DMSO-d6): δ 167.9 (C=O), 155.0 (C4
2-[4-(2-Hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl]-N-
methyl-N-phenylpropanamide (5d): White solid; Yield:

Vol. 29, No. 10 (2017)
Synthesis and Microbicidal Activity of Substituted 1,2,3-Triazoles having Amide and Hydroxy Functionality 2151
triazole), 141.0, 130.5, 129.0, 128.8, 120.6 (C5 triazole), 70.2,
55.6, 44.5, 35.9, 28.6, 18.5, 12.9, 8.8; HRMS (m/z) calculated
for C17H24N4O2 [M+H]+: 317.1899. Found: 317.1970.
Growth was assessed after incubation for 24 h at 37 °C in case
of all bacteria, for 48 h at 25 °C in case of C. albicans and for
120 h at 25 °C for in case of A. niger and the minimum inhibitory
concentration (MIC) value was noted. The MIC is defined as
the lowest concentration of the antimicrobial agent that prevents
visible growth of a microorganism under defined conditions.
2-[4-(2-Hydroxybutan-2-yl)-1H-1,2,3-triazol-1-yl]-
N,N-diphenylpropanamide (5i): White solid; Yield: 86 %;
m.p. 76-80 °C; IR (KBr, νmax, cm-1): 3370 (O-H str.), 3159
(C-H str. triazole), 3061 (C-H str. aromatic ring), 2972 (C-H
str., aliphatic), 1678 (C=O str. amide), 1593, 1454 (C=C str.,
RESULTS AND DISCUSSION
1
aromatic ring); H NMR (400 MHz, DMSO-d6): δ 7.79 (s,
2-Bromopropanoyl bromide (2) was added in aromatic
amines (1a-1c) in dichloromethane using potassium carbonate
as a base to synthesize 2-bromo-N-substituted-N-phenylpro-
panamides (3a-3c). 1,4-Disubstituted 1,2,3-triazoles (5a-5i)
were synthesized by reacting 2-azido-N-substituted-N-phenyl-
propanamides (generated in situ from 2-bromo-N-substituted
N-phenylpropanamides and sodium azide) with hydroxyl terminal
alkynes using dimethylformamide:water as solvent in the
presence of copper sulphate pentahydrate and sodium ascorbate
with stirring of 8-10 h at 35-50 °C (Scheme-I).
1H, C-H triazole), 7.43 (brs, 10H, Ar-H), 5.46 (q, 1H, J = 4.8
Hz), 4.94 (s, 1H, OH), 1.75-1.64 (m, 5H), 1.42 (s, 3H), 0.75
(t, 3H, J = 8 Hz); 13C NMR (100 MHz, DMSO-d6): δ 168.8
(C=O), 155.0 (C4 triazole), 130.6, 129.6, 129.0, 127.3, 120.8
(C5 triazole), 70.2, 56.2, 36.0, 28.7, 18.5, 8.8; HRMS (m/z) calcu-
lated for C21H24N4O2[M+H]+: 365.1899. Found: 365.1968.
Antimicrobial activity: Compounds (5a-5i) were screened
for in vitro antimicrobial activity against Escherichia coli,
Enterobacter aerogenes, Klebsiella pneumoniae, Staphylo-
coccus aureus, Candida albicans and Aspergillus niger by
serial dilution method using a stock solution of 100 µg/mL
concentration in five sets at different concentrations of 50, 25,
12.5, 6.25, 3.12 µg/mL. DMSO used as control solvent while,
norfloxacin and fluconazole used as standard drugs, respec-
tively for bacteria and fungus.All these dilutions were inoculated
with respective bacterial and fungal strain in saline solution.
The characterization of synthesized compounds was carried
out by the techniques FTIR, 1H NMR, 13C NMR spectroscopy
and HRMS. The triazole formation was confirmed by the
presence of absorption bands in the region 3384-3370 (O-H
str.), 3172-3140 (C-H, str., triazole ring), 1678-1662 (C=O
1
str., amide) cm-1 in IR spectra. The H NMR spectra of the
O
1
1
R
H
R
Br
N
N
Br
K2CO3, DCM
0-5 ºC
+
Br
O
(2)
(1a-1c)
(3a-3c)
1a, 3a: R = CH
1
1b, 3b:
3
R = C H -
1
1c, 3c: R = C H -
2 5
1
6 5
O
O
1
R
1
N
R
Br
N
2
N
NaN3, CuSO4.5H2O
Sodium ascorbate
R
3
N
R
3
N
R
2
R
+
HO
OH
DMF/ H2O (8:2)
35-50 ºC, 8-10 h
(3a-3c)
(4a-4c)
(5a-5i)
4a: R = H, R = H
2
3
4b:
R = CH -, R = CH -
2
4c: R = CH -, R = C H -
3
3
3
2
3
3
2
5
Compound
R1
CH3
R2
R3
Compound
5f
R1
R2
R3
5a
5b
5c
5d
5e
H
H
H
H
C6H5
CH3
C2H5
C6H5
CH3
CH3
CH3
CH3
CH3
C2H5
C2H5
C2H5
C2H5
C6H5
CH3
H
5g
5h
5i
H
CH3
CH3
CH3
CH3
C2H5
Scheme-I

2152 Kaushik et al.
Asian J. Chem.
TABLE-2
ANTIFUNGAL ACTIVITY OF 1,4-DISUBSTITUTED
1,2,3-TRIAZOLES (5a-5i) (MIC IN µmol/mL)
compounds 5a-5i displayed one characteristic singlet in the
region at δ 7.97-7.76 due to triazolyl proton. In the 13C NMR
spectra signal for C4 of the triazole moiety appeared in the
region at δ 156.0-148.1, for C5 signal appeared in region δ
119.7-122.3 and signals due to carbonyl carbons of amide
appeared in range of δ 168.9-167.9.
C. albicans
(MTCC 227)
A. niger
(MTCC 282)
Compound
5a
0.0957
0.0911
0.0775
0.0864
0.0826
0.0713
0.0824
0.0790
0.0343
0.0408
0.0957
0.0911
0.0775
0.0864
0.0413
0.0356
0.0824
0.0790
0.0343
0.0102
5b
Antibacterial activity: All the synthesized compounds
(5a-5i) were tested for in vitro antibacterial activity against
Gram-negative bacteria - Escherichia coli (MTCC 443),
Enterobacteraerogenes (NCDC 106), Klebsiella pneumoniae
(NCDC 138) and Gram-positive bacteria - Staphylococcus aureus
(MTCC 3160) by the standard serial dilution method [22].
The minimum inhibitory concentration values (MIC; corres-
ponds to the lowest concentration that inhibits the microbial
growth) of the synthesized triazoles are represented in µmol/mL
and the results were compared to the control drug norfloxacin
(Table-1).The screening results revealed that the compound
5f and 5i was found to be the broadly active against bacterial
strains amongst tested compounds, while compounds 5c, 5f,
5h and 5i showed excellent activity comparable to standard
against S. aureus.
5c
5d
5e
5f
5g
5h
5i
Fluconazole
Conclusion
In the present study, regioselective synthesis of a series
of 2-(4-(hydroxyalkyl)-1H-1,2,3-triazol-1-yl)-N-substituted
N-phenylpropanamide employing click reaction has been
reported. Efficient 1,3-dipolar cycloaddition between terminal
hydroxyalkynes and 2-azido-N-substituted N-phenylpro-
panamides yielded 1,4-disubstituted 1,2,3-triazole having amide
and hydroxy functionality in good yield. Some of the synthesized
compound also displayed appreciable microbicidal activity.
TABLE-1
ANTIBACTERIAL ACTIVITY OF 1,4-DISUBSTITUTED
1,2,3-TRIAZOLES (5a-5i) (MIC IN µmol/mL)
E. K.
aerogenes pneumoniae
E. coli
(MTCC
443)
S. aureus
(MTCC
3160)
REFERENCES
Compd.
(NCDC
106)
(NCDC
138)
1. J. de O. Santos, G.R. Pereira, G.C. Brandao, T.F. Borgati, L.M.Arantes,
R.C. de Paula, L.F. Soares, M.F.A. do Nascimento, M.R.C. Ferreira, A.G.
Taranto, F.P. Varottig and A.B. de Oliveira, J. Braz. Chem. Soc., 27,
551 (2016);
5a
0.1914
0.1822
0.1555
0.1729
0.0826
0.0713
0.0824
0.0790
0.0685
0.0391
0.0957
0.0911
0.0777
0.0864
0.0826
0.0713
0.0824
0.0790
0.0685
0.0391
0.0957
0.0911
0.0777
0.0864
0.0826
0.0713
0.0824
0.0790
0.0685
0.0391
0.1914
0.1822
0.0777
0.1729
0.0826
0.0713
0.1649
0.0790
0.0685
0.0783
5b
5c
https://doi.org/10.5935/0103-5053.20150287.
5d
2. H.M. Faidallah, S.S. Panda, J.C. Serrano,A.S. Girgis, K.A. Khan, K.A.
Alamry, T. Therathanakorn, M.J. Meyers, F.M. Sverdrup, C.S. Eickhoff,
S.G. Getchell and A.R. Katritzky, Bioorg. Med. Chem. Lett., 24, 3527
(2016);
5e
5f
5g
5h
5i
https://doi.org/10.1016/j.bmc.2016.05.060.
3. N. Dubey, M.C. Sharma, A. Kumar and P. Sharma, Med. Chem. Res.,
24, 2717 (2015);
https://doi.org/10.1007/s00044-015-1329-5.
Norfloxacin
It is quite clear from antibacterial assay that in the target
compounds N,N-diphenyl substituted triazole (5g-5i) derivatives
possess an upper hand in activity than the N-ethyl-N-phenyl/
N-methyl-N-phenyl derivatives whereas the presence of alkyl
group on carbon having free hydroxyl group in the synthesized
triazoles increases the antibacterial activity.
4. T.B. Cassamale, E.C. Costa, D.B. Carvalho, N.S. Cassemiro, C.C.
Tomazela, M.C.S. Marques, M. Ojeda, M.C.F. Matos, S. Albuquerque,
C.C.P.Arrudab andA.C.M. Baroni, J. Braz. Chem. Soc., 27, 1217 (2016);
https://doi.org/10.5935/0103-5053.20160017.
5. P. Sambasiva Rao, C. Kurumurthy, B.Veeraswamy, G. Santhosh Kumar,
Y. Poornachandra, C. Ganesh Kumar, S.B. Vasamsetti, S. Kotamraju and
B. Narsaiah, Eur. J. Med. Chem., 80, 184 (2014);
https://doi.org/10.1016/j.ejmech.2014.04.052.
Antifungal activity: The synthesized 1,4-disubstituted
1,2,3-triazoles (5a-5i) were studied for in vitro antifungal activity
against two fungal strains-Candida albicans (MTCC 227) and
Aspergillus niger (MTCC 282) using serial dilution method
[22]. Fluconazole was used as the standard. The minimum
inhibitory concentration (MIC) values were recorded in µmol/
mL (Table-2). In vitro antifungal studies revealed that the
compounds 5f and 5i displayed significant activity while the
rest of the compounds showed moderate to low activity.
The structure-activity relationship study revealed that
antifungal screening of synthesized compounds increases on
replacement of methyl/ethyl group present on N of aniline by
phenyl group and also the substitution of hydrogen by alkyl
group on the carbon bearing hydroxy group, increases the anti-
fungal activity in the synthesized compounds.
6. Y.Ali, M.S.Alam, H. Hamid,A. Husain, S. Bano,A. Dhulap, C. Kharbanda,
S. Nazreen and S. Haider, Eur. J. Med. Chem., 92, 490 (2015);
https://doi.org/10.1016/j.ejmech.2015.01.001.
7. C.P. Kaushik, R. Luxmi, D. Singh and A. Kumar, Mol. Divers., 21, 137
(2017);
https://doi.org/10.1007/s11030-016-9710-y.
8. P. Salehi, K. Babanezhad-Harikandei, M. Bararjanian, A. Al-Harrasi,
M.A. Esmaeili and A. Aliahmadi, Med. Chem. Res., 25, 1895 (2016);
https://doi.org/10.1007/s00044-016-1622-y.
9. C.P. Kaushik, A. Pahwa, R. Thakur and P. Kaur, Synth. Commun., 47,
368 (2017);
https://doi.org/10.1080/00397911.2016.1265983.
10. Q. Li, W. Tan, C. Zhang, G. Gu and Z. Guo, Int. J. Biol. Macromol., 91,
623 (2016);
https://doi.org/10.1016/j.ijbiomac.2016.06.006.
11. Z.C. Dai,Y.F. Chen, M. Zhang, S.K. Li, T.T.Yang, L. Shen, J.X. Wang,
S.-S. Qian, H.-L. Zhu andY.-H.Ye, Org. Biomol. Chem., 13, 477 (2015);
https://doi.org/10.1039/C4OB01758G.

Vol. 29, No. 10 (2017)
Synthesis and Microbicidal Activity of Substituted 1,2,3-Triazoles having Amide and Hydroxy Functionality 2153
12. C.P. Kaushik, K. Kumar, B. Narasimhan, D. Singh, P. Kumar and A.
Pahwa, Monatsh. Chem., 148, 765 (2017);
https://doi.org/10.1007/s00706-016-1766-y.
18. M. Huang, Z. Deng, J. Tian and T. Liu, Eur. J. Med. Chem., 127, 900 (2017);
https://doi.org/10.1016/j.ejmech.2016.10.067.
19. R. Huisgen, in ed.: A. Padwa, 1,3-Dipolar Cycloaddition Chemistry,
Wiley, New York, vol. 1, Chap. 1, pp. 1-176 (1984).
20. H.C. Kolb, M.G. Finn and K.B. Sharpless, Angew. Chem. Int. Ed., 40,
2004 (2001);
13. H.N. Nagesh, N. Suresh, G.V.S.B. Prakash, S. Gupta, J.V. Rao and
K.V.G.C. Sekhar, Med. Chem. Res., 24, 523 (2015);
https://doi.org/10.1007/s00044-014-1142-6.
14. R. Raj, V. Sharma, M.J. Hopper, N. Patel, D. Hall, L.A. Wrischnik, K.M.
Land and V. Kumar, Med. Chem. Res., 23, 3671 (2014);
https://doi.org/10.1007/s00044-014-0956-6.
https://doi.org/10.1002/1521-3773(20010601)40:11<2004::AID-
ANIE2004>3.0.CO;2-5.
21. C.W. Tornøe, C. Christensen and M. Meldal, J. Org. Chem., 67, 3057 (2002);
https://doi.org/10.1021/jo011148j.
15. L. Pulipati, P.Yogeeswari, D. Sriram and S. Kantevari, Bioorg. Med. Chem.
Lett., 26, 2649 (2016);
https://doi.org/10.1016/j.bmcl.2016.04.015.
22. C.P. Kaushik, K. Kumar, S.K. Singh, D. Singh and S. Saini, Arab. J.
Chem., 9, 865 (2016);
https://doi.org/10.1016/j.arabjc.2013.09.023.
16. A. Anand, M.V. Kulkarni, S.D. Joshi and S.R. Dixit, Bioorg. Med. Chem.
Lett., 26, 4709 (2016);
https://doi.org/10.1016/j.bmcl.2016.08.045.
17. R.R. Ruddarraju, A.C. Murugulla, R. Kotla, M.C. Babu Tirumalasetty,
R. Wudayagiri, S. Donthabakthuni, R. Maroju, K. Baburao and L.S. Parasa,
Eur. J. Med. Chem., 123, 379 (2016);
https://doi.org/10.1016/j.ejmech.2016.07.024.