Synthesis and antimicrobial screening of some novel 2-(5-(4-(1H-benzo[d][1, 2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenols incorporated by triazole moiety

Article abstract of DOI:10.1002/jhet.1646

A novel series of 2-(5-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5- dihydro-1H-pyrazol-3-yl)phenols derivative has been synthesized from (E)-3-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-1-(2-hydroxyphenyl) prop-2-en-1-ones in ethanol and hydrazine hydrate under reflux condition. The synthesized compounds were screened for antibacterial activity against Gram-positive bacteria viz Staphylococcus aureus and Bacillus subtilis and Gram-negative bacteria viz Escherichia coli and Salmonella typhi, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, ¹H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.

Full text of DOI:10.1002/jhet.1646

March 2014
Synthesis and Antimicrobial Screening of Some Novel
513
2
-(5-(4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-
3
-yl)phenols Incorporated by Triazole Moiety
Mohammad U. Shaikh, Ganesh R. Jadhav, Rajesh P. Kale, Asha V. Chate,
Deepak R. Nagargoje,* and Charansingh H. Gill
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, M.S 431 004, India
*
E-mail: dnagargoje@gmail.com
Received November 21, 2011
DOI 10.1002/jhet.1646
Published online 11 November 2013 in Wiley Online Library (wileyonlinelibrary.com).
K
2
CO
3
, DMF
+
F
CHO
8
0oC
N
CHO
NH
N
N
N
N
2
3
1
R
1
OH
O
Aq. KOH
Ethanol
R
2
4
(a-h)
N
R
1
N
N
N
N
R
1
OH
N
OH
O
N
NH
2 2
NH
Ethanol
R
2
R
2
NH
6
(a-h)
5 (a-h)
A novel series of 2-(5-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenols derivative
has been synthesized from (E)-3-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-1-(2-hydroxyphenyl)prop-2-
en-1-ones in ethanol and hydrazine hydrate under reflux condition. The synthesized compounds were screened
for antibacterial activity against Gram-positive bacteria viz Staphylococcus aureus and Bacillus subtilis and
Gram-negative bacteria viz Escherichia coli and Salmonella typhi, respectively. Some of the tested compounds
1
showed significant antimicrobial activity. IR, H NMR, mass spectral data, and elemental analysis elucidated
the structures of all the newly synthesized compounds.
J. Heterocyclic Chem., 51, 513 (2014).
INTRODUCTION
ergosterol, the major steroid in fungal membranes, by
blocking 14-a-demethylation, which occurs with accumula-
tion of 14-a-methyl steroids and disruption of the fungal
membranes [12–14]. Fluconazole causes second bronchial
arch anomalies in mice [15].
Azoles are found widely in natural sources and there
are several drugs available that contain azole ring. Triazoles
are important five-membered heterocyclic rings. Triazoles
N
N
N
N
N
F
O
N
O
N
N
N
N
N
O
O
N
N
N
F
OH
H
Cl
Cl
1.Itraconazole.
2.Fluconazole
are basically of three types, that is, 1,2,3-triazole; 1,2,4-tria-
zole; and 1,2,3-benzotriazole. The 1H-1,2,4-triazoles are
considered interesting heterocycles because they possess im-
portant pharmacological activities such as antifungal and
antiviral. Examples of antifungal drugs [1,2] are fluconazole
2-Pyrazoline ring system has attracted significant
interest in organic and medicinal chemistry over the
past few decades. Scaffolds containing the 2-pyrazoline
(4, 5-dihydropyrazole) heterocyclic have demonstrated a
wide range of biological activities, including anticancer
activity through the inhibition of kinesin spindle pro-
tein [16], CB1 receptor antagonism for obesity [17], mono-
amine oxidase inhibition for depression [18], and a host of
[3,4], itraconazole [5], ravuconazole [6], voriconazole [7–9],
ICI 153066 [10], and posaconazole [11]. The action of these
compounds is based on the inhibition of biosynthesis of
©
2013 HeteroCorporation

5
14
M. U. Shaikh, G. R. Jadhav, R. P. Kale, A. V. Chate, D. R. Nagargoje, and C. H. Gill
Vol 51
Scheme 1. Synthesis of chalcones and pyrazolines.
K
2
CO
3
, DMF
+
F
CHO
8
0oC
N
CHO
NH
N
N
N
N
2
3
1
R
1
OH
O
Aq. KOH
Ethanol
R
2
4
(a-h)
N
R
1
N
N
N
N
R
1
OH
N
OH
O
N
NH
2 2
NH
Ethanol
R
2
R
2
NH
6
(a-h)
5 (a-h)
other antibacterial and antiviral agents [19]. Some of the
pyrazoline derivatives are reported to possess antidiabetic
and antidepressant properties [20]. Pyrazoline derivatives find
applications as dyestuffs, analytical reagents, and agrochem-
icals [21]. Also the pyrazoline derivatives possess pronounced
anti-inflammatory activity [22–24].
Therefore, in view of these important biological activities
of both the scaffolds, and in continuation of our research
program [25–29], we report the synthesis of some new
The purity of compounds was checked by TLC. Analytical
1
and spectral data (IR, H NMR, mass, and elemental analysis)
of the newly synthesized compounds were in full agreement
with the proposed structure. The structure of 5a is interpreted
from spectroscopic data. The IR spectrum of 5a showed a
À1
characteristic absorption band at 3334 and 1676 cm due to
1
-OH and C═O stretching. Its H NMR spectrum exhibits
presence of olefinic protons as a doublet at d = 7.9 and 8.2
regions with a mutual coupling constant value (J= 15.6 and
15.6 Hz). These observed coupling constant values indicate
the presence of E-configuration from the structure and the
remaining aromatic protons appear at their respective
positions. The phenolic -OH is highly deshielded and appears
at d = 12.40 ppm. Mass spectrum of (E)-1-(2-hydroxyphenyl)-
3-(4-(phenylthio)phenyl)prop-2-en-1-one(E)-3-(4-(1H-benzo
1H-1,2,4-triazoles-incorporated pyrazolines derivatives from
the chalcones and tested the antibacterial and antifungal
activities of the new resulting compounds, which have been
found to possess an interesting profile of pharmacological
activity, against representative Gram-negative and Gram-
positive bacteria and fungi.
[
1
d][1,2,3]triazol-1-yl)phenyl)-1-(2-hydroxyphenyl)prop-2-en-
-one showed (M ) peak at 342 and (M ) peak at 340. The
+
À
RESULT AND DISCUSSION
IR spectra of prepared 6a revealed the absorption band
À1
Chemistry. The synthetic route for the preparation of 2-
5-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-
at 3238 cm due to -OH stretching and also exhibited
À1
(
C═N stretching vibrations in the region 1522 cm , and
1
H-pyrazol-3-yl)phenol is shown in Scheme 1. 1H-Benzo
compound 6a showed an additional absorption band at
À1
1
[
d][1,2,3]triazole (1) treated with 4-flurobenzaldehyde (2)
3058 cm characteristic for pyrazole NH. In H NMR spec-
tra of compounds 6a showed three multiplets at d 3.06, 3.67
and 4.97 ppm that resulted from the AMX pattern displayed
by two diastereotopic protons at C-4 (H and H ) and one
ꢀ
in DMF and K CO at 80 C to yield 4-(phenylthio)
2
3
benzal4-(1H-benzo[d][1,2,3]triazol-1-yl)benzaldehyde
3). The 4-(phenylthio)benzal4-(1H-benzo[d][1,2,3]triazol-
-yl)benzaldehyde (3) was subjected to base-catalyzed
(
1
a
b
proton (H ) at C-5. One singlet proton at 11.13ppm due to
c
Claisen–Schmidt condensation reaction [30] with appropriate
o-hydroxy acetophenones (4a–h) generating (E)-1-(2-
hydroxyphenyl)-3-(4-(phenylthio)phenyl)prop-2-en-1-one(E)-3-
-OH and the rest of the aromatic proton appear at their
respective position and exhibit one doublet at 7.99ppm due
to NH. Mass spectrum of preparation 2-(5-(4-(1H-benzo[d]
[1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)
(
4-(1H-enzo[d][1,2,3]triazol-1-yl)phenyl)-1-(2-hydroxyphenyl)
prop-2-en-1-one (5a–h). 2-(5-(4-(1H-Benzo[d][1,2,3]triazol-
-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol (6a–h) was
prepared by the oxidative cyclization of corresponding
E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio) phenyl)prop-2-
en-1-one(E)-3-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-1-
2-hydroxyphenyl)prop-2-en-1-one (5a–h) in ethanol and
hydrazine hydrate under reflux condition.
+
À
phenol showed (M ) peak at 356.2 and (M ) at 354.2.
1
CONCLUSION
(
In summary, we have synthesized a series of benzotriazole-
incorporated novel (E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)
phenyl)prop-2-en-1-one(E)-3-(4-(1H-benzo[d][1,2,3]
(
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2014
Triazole Containing Novel 2-(5-(4-(1H-Benzo[d]
515
[1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenols
Table 1
triazol-1-yl)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one and
2-(5-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-
Physical data of the compounds (5a–h) and (6a–h).
1
H-pyrazol-3-yl)phenol derivatives, and their antimicrobial
ꢀ
mp ( C)
Compound
R
1
R
2
Yield (%)
activities have been evaluated. All the compounds demo-
strated potent inhibition against all the tested strains. The
importance of such work lies in the possibility that the
new compounds might be more efficacious drugs
against bacteria, which could be helpful in designing more
potent antibacterial agent for therapeutic use. The structure
of the synthesized compounds was confirmed with their
spectral data.
5a
H
H
CH
Cl
H
H
CH
H
H
H
CH
Cl
H
H
CH
H
H
Cl
74
72
60
63
65
70
64
68
67
65
50
61
53
64
58
66
134–136
137–139
155–157
156–158
148–150
169–171
158–160
132–134
143–145
146–148
165–167
172–174
160–162
184–186
149–151
139–141
5
5
5
5
b
c
d
e
3
3
3
3
CH
Cl
CH
Br
Cl
F
3
3
5f
5
5
6
6
6
6
6
6
6
6
g
h
a
b
c
d
e
f
g
h
H
Cl
CH
Cl
CH
Br
Cl
F
3
3
EXPERIMENTAL
The melting points of all synthesized compounds were
determined in open capillary tubes and are uncorrected. The
purity of all compounds was checked by TLC. IR spectra were
1
recorded on Jasco FT-IR-4100 in KBr disk (Tokyo, Japan). H
NMR spectra were recorded on a Varian As 400 MHz spectrom-
eter in CDCl /DMSO-d (Palo Alto, CA); chemical shifts (d) are
3
6
in parts per million (ppm) relative to TMS and coupling constant
(
J) are expressed in hertz (Hz). Mass spectra were recorded on a
(E)-3-(4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl)-1-(5-chloro-
À1
Macro mass spectrometer (Waters, Milford, MA) by electro-spray
method (ES). Elemental analysis was performed on Perkin-Elmer
EAL-240 elemental analyzer (Waltham, MA).
2-hydroxyphenyl)prop-2-en-1-one (5b). IR (KBr) cm : 3330 (OH),
1
1672 (C═O), 1520 (C═C); H NMR (400 MHz, DMSO-d
):
6
d 7.000–7.043 (m, 2H, aromatic); 7.5213–7.620 (m, 1H, aromatic);
7.686–7.712 (m, 1H, aromatic); 7.942–7.979 (d, J= 15.4 Hz, 1H,
ethylenic); 8.345–8.384 (d, J= 15.5 Hz, 1H, ethylenic); 8.006–8.038
(m, 3H, aromatic); 8.163–8.169 (m, 3H, aromatic); 8.294–8.316
Synthesis of 4-(1H-benzo[d][1,2,3]triazol-1-yl) benzaldehyde
(
8
3). 1,2,3-Benzotriazole (1) was dissolved in DMF (1.0 g,
.4 mmol). To this solution, K CO (2.3 g, 16.8 mmol) was added
2
3
ꢀ
+
and heated at 80 C with stirring. After 30 min. (1 mL, 8.4 mmol)
4
8
(dd, 1H, aromatic); 12.35 (s, 1H, -OH); EC–MS: 376.3 (M ),
1
-fluorobenzaldehyde (2) was added and heating continued for
–10h. On completion of reaction, the reaction mixture was
374.21 (M ); Anal. Calcd. for C, 67.20; H, 3.73; N, 11.2; Found: C,
67.21; H, 3.76; N, 11.24.
cooled and added dropwise to ice water. The separated product
3) was filtered and dried. The product obtained was pure and
used further without any purification.
(E)-3-(4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl)-1-(2-hydroxy-
À1
(
3,5-dimethylphenyl)prop-2-en-1-one (5c). IR (KBr) cm : 3340
1
(OH), 1679 (C═O), 1528 (C═C).; H NMR (400 MHz, DMSO-d
6
):
General procedure for the synthesis of (E)-1-(2-
hydroxyphenyl)-3-(4-(phenylthio) phenyl)prop-2-en-1-one(E)-
d 2.34 (s, 3H, CH3), 2.46 (s, 3H, CH3), 6.924–6.939
(d, 1H, aromatic); 7.224–7.260 (d, 1H, aromatic); 7.943–7.972
(d, J= 15.5 Hz, 1H, ethylenic); 8.325–8.374 (d, J=15.4Hz, 1H,
ethylenic); 8.106–8.138 (m, 4H, aromatic); 8.353–8.399 (m, 4H,
3
-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-1-(2-hydroxyphenyl)
prop-2-en-1-one (5a–h). An aqueous solution of KOH (0.410 g,
.8 mmol) was added to a suspension of 1-(2-hydroxyphenyl)
+
À
2
aromatic); 12.42 (s, 1H, -OH); EC–MS: 370.25 (M ), 368.43 (M );
Anal. Calcd. for C, 74.8; H, 4.88; N, 11.38; Found: C, 74.82; H,
4.89; N, 11.40.
ethanone (4g) (0.500 g, 1.4 mmol) and 4-(1H-benzo[d][1,2,3]
triazol-1-yl)benzaldehyde (3) (0.326 g, 1.4 mmol) in 10 mL
ethanol–water mixture. The mixture was stirred at room
temperature for overnight. The mixture was poured into water
and acidified with HCl (2 M) till pH = 4. The solid product (6g)
separated out was filtered off and crystallized from ethanol.
The compounds (6a–h) were prepared by following the
aforementioned procedure. Their structures have been
(E)-3-(4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl)-1-(3,5-dichloro-
À1
2-hydroxyphenyl)prop-2-en-1-one (5d). IR (KBr) cm : 3344
1
(OH), 1671 (C═O), 1530 (C═C).; H NMR (400 MHz, DMSO-d ):
6
d 7.314–7.341 (d, 1H, aromatic); 7.561–7.6010 (d, 1H, aromatic);
7.776–7.742 (m, 4H, aromatic); 7.943–7.979 (d, J= 15.6 Hz, 1H,
ethylenic); 8.445–8.464 (d, J= 15.6 Hz, 1H, ethylenic); 8.253–8.299
(m, 4H, aromatic); 8.284–8.306 (dd, 1H, aromatic); 12.38 (s,
1
confirmed by mass, IR, and H NMR spectra (Table 1).
+
(
E)-1-(2-Hydroxyphenyl)-3-(4-(phenylthio) phenyl)prop-2-
1H, -OH); EC–MS: 410.1 (M ); Anal. Calcd. for C, 61.61; H, 3.42;
en-1-one(E)-3-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-1-(2-
hydroxyphenyl)prop-2-en-1-one (5a). IR (KBr) cm : 3334 (OH),
N, 10.27; Found: C, 61.60; H, 3.44; N, 10.26.
À1
General procedure for the synthesis of 2-(5-(4-(1H-benzo[d]
[1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol
(6a–h). Chalcone (5g) (0.1 g, 0.29 mmol) was dissolved in 2 mL of
ethanol. To this reaction mixture, hydrazine hydrate (0.014mL,
2.9 mmol) was added. The reaction mass was heated at reflux for
4 h. After completion of reaction (checked by TLC), reaction
mixture was cooled to room temperature. At the end, 10 mL cold
water was slowly added to the flask, and the separated product
(6g) was filtered and washed with cold water and crystallized
1
1
7
7
1
8
8
676 (C═O), 1524 (C═C); H NMR (400 MHz, DMSO-d
6
): d
.004–7.041 (m, 2H, aromatic); 7.521–7.600 (m, 2H, aromatic);
.676–7.712 (m, 1H, aromatic); 7.933–7.972 (d, J = 15.6Hz,
H, ethylenic); 8.245–8.284 (d, J = 15.6 Hz, 1H, ethylenic);
.006–8.038 (m, 3H, aromatic); 8.153–8.199 (m, 3H, aromatic);
.284–8.306 (dd, 1H, aromatic); 12.40 (s, 1H, -OH); EC–MS: 342
+
À
(
M ), 340 (M ); Anal. Calcd. for C, 73.90; H, 4.40; N, 12.32;
Found: C, 73.86; H, 4.45; N, 12.35.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

5
16
M. U. Shaikh, G. R. Jadhav, R. P. Kale, A. V. Chate, D. R. Nagargoje, and C. H. Gill
Vol 51
from ethanol. The compounds (6a–h) were prepared by following
2-(5-(4-(1H-benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-
À1
the aforementioned procedure. Their structures have been
1H-pyrazol-3-yl)-4,6-dichlorophenol (6d). IR (KBr) cm
:
1
1
confirmed by mass, IR, and H NMR spectra.
32342 (OH), 3063 (NH), 1531 (C═N); 1127 (C-N); H NMR
(400 MHz, DMSO-d ): d 3.19–3.21 (m, 1H, C Pyrazoline); 3.71–
3.74 (m, 1H, C Pyrazoline); 4.99–5.07 (m, 1H, chiral Pyrazoline);
2
-(5-(4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-
6
4
À1
1
3
H-pyrazol-3-yl)phenol (6a). IR (KBr) cm : 3238(OH),
058 (NH), 1522 (C═N); 1118 (C-N); H NMR (400 MHz,
4
1
6.94–6.98 (d, 1H, aromatic); 7.50–7.98 (m, 8H, aromatic); 8.36–
8.39 (d, J= 12.2 Hz, 1H, aromatic); 8.00–8.12 (d, 1H, NH);
DMSO-d ): d 3.06–3.13 (m, 1H, C Pyrazoline); 3.67–3.74
6
4
+
(
m, 1H,
C
4
Pyrazoline); 4.97–5.03 (m, 1H, chiral
11.1343 (s, 1H, -OH); EC–MS: 424.1 (M ); Anal. Calcd. for C,
Pyrazoline); 6.87–6.92 (m, 2H, aromatic); 7.20–7.93 (m,
59.57; H, 3.54; N, 16.55; Found: C, 59.59; H, 3.55; N, 16.57.
8
8
H, aromatic); 8.16–8.19 (d, J = 12 Hz, 2H, aromatic); 7.99–
Biological assay.
Some of the synthesized compounds
+
.00 (d, 1H, NH); 11.13 (s, 1H, -OH); EC–MS: 356.2 (M )
were screened for in vitro antibacterial activities against Gram-
positive and Gram-negative bacteria. In Gram-positive bacteria,
Staphylococcus aureus and Bacillus subtilis were used and in
Gram-negative Escherichia coli and Salmonella typhi were used
against standard tetracyclin and ampicillin. The antibacterial
activities were carried out on nutrient agar with standard
composition and by standard procedure of paper disk method [31].
Petri dishes and necessary glasswares were sterilized in hot air
À
and 354.2 (M ); Anal. Calcd. for C, 70.98; H, 4.78; N,
1
9.71; Found: C, 70.95; H, 4.80; N, 19.78.
2
-(5-(4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-
À1
pyrazol-3-yl)-4-chlorophenol (6b). IR (KBr) cm : 3242 (OH),
1
3
052 (NH), 1527 (C═N); 1128 (C-N); H NMR (400 MHz,
DMSO-d ): d 3.16–3.19 (m, 1H, C Pyrazoline); 3.70–3.748
m, 1H, C Pyrazoline); 4.99–5.00 (m, 1H, chiral Pyrazoline);
6
4
(
4
ꢀ
oven (190 C, 45 min). The nutrient agar and saline (0.82% NaCl)
6
8
.90–6.96 (m, 2H, aromatic); 7.25–7.97 (m, 7H, aromatic);
ꢀ
were sterilized in autoclave (121 C, 15 psi, 20 min). Inoculum was
.18–8.20 (d, J = 12.1 Hz, 2H, aromatic); 8.00–8.10 (d, 1H,
+
prepared in sterile saline, and optical density of all pathogens was
adjusted to 0.10 at 625 nm on Chemito Spectrascan UV 2600
spectrophotometer (Mumbai, India), which is equivalent to 0.5
McFarland standards. The nutrient agar plates were prepared by
pour plate method [32]. The sensitivity of the compounds was
tested by disk diffusion method (paper disk method). All the
bacterial cells were cultured in nutrient plates and the compounds
to be tested were dissolved in DMSO solvent and were soaked on
paper disks. The disks were placed into the plates and incubated at
NH); 11. 45 (s, 1H, -OH); EC–MS: 380.4 (M ) and 378.3
À
(
M ); Anal. Calcd. for C, 64.78; H, 4.11; N, 17.99; Found: C,
6
4.75; H, 4.13; N, 17.97.
2
-(5-(4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-
À1
1
H-pyrazol-3-yl)-4,6-dimethylphenol (6c). IR (KBr) cm
:
1
3
234 (OH), 3061 (NH), 1526 (C═N); 1124 (C-N); H NMR
(
400 MHz, DMSO-d ): d 2.42 (s, 3H, CH ), 2.51 (s, 3H, CH ),
6 3 3
3
.09–3.14 (m, 1H, C4 Pyrazoline); 3.69–3.77 (m, 1H, C4
Pyrazoline); 4.99–5.05 (m, 1H, chiral Pyrazoline); 6.94–6.97
ꢀ
(
(
(
m, 2H, aromatic); 7.50–7.98 (m, 8H, aromatic); 8.26–8.29
d, J = 12.4 Hz, 2H, aromatic); 8.00–8.12 (d, 1H, NH); 11.1343
s, 1H, -OH); EC–MS: 356.2 (M ) and 354.2 (M ); Anal.
37 C for 24 h. The diameter in millimeter of zone of inhibition
around each disk was measured by scale, and the observed data of
antimicrobial activity of compounds and the standard drugs are
given in Table 2. Among all the compounds screened, 5e, 5f, 6d,
6f, and 6g showed good antibacterial activity against Gram-positive
+
À
Calcd. for C, 72.75; H, 5.23; N, 18.32; Found: C, 72.74; H,
.24; N, 18.31.
5
Table 2
Antimicrobial activity of compounds (5a–h) and (6a–h).
Gram-positive
Gram-negative
Salmonella typhi
Entry
Staphylococcus aureus
Bacillus subtilis
Escherichia coli
5
5
5
5
5
5
5
5
6
6
6
6
6
6
6
6
a
b
c
d
e
18
20
—
21
29
27
22
22
20
—
—
21
22
30
25
19
35
32
20
25
—
21
28
19
20
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Ampicillin
Tetracyclin
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2014
Triazole Containing Novel 2-(5-(4-(1H-Benzo[d]
517
[1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenols
bacteria, and compounds 5b, 5d, 5g, 6b, 6d, and 6e showed good
activity against Gram-negative bacteria as comparable with that of
standard drug tested. So the result of all preliminary studies indicated
that the substituted (E)-1-(2-hydroxyphenyl)-3-(4-(phenylthio)
phenyl)prop-2-en-1-one(E)-3-(4-(1H-benzo[d][1,2,3]triazol-1-yl)
phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one and 2-(5-(4-(1H-
benzo[d][1,2,3]triazol-1-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)
phenol moiety represent a new class of pharmacophore for broad
spectrum antimicrobial activity.
[16] Coleman, P. J.; Schreier, J. D.; Cox, C. D.; Fraley, M. E.;
Garbaccio, R. M.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Lobell,
R. B.; Rickert, K.; Tao, W.; Diehl, R. E.; South, V. J.; Davide, J. P.; Kohl,
N. E.; Yan, Y.; Kuo, L.; Prueksaritanont, T.; Li, C.; Mahan, E. A.;
Fernandez-Metzler, C.; Salata, J. J.; Hartman, G. D. Bioorg Med Chem
Lett 2007, 17, 5390.
[17] Lange, J. H. M.; Van Stuivenberg, H. H.; Veerman, W.; Wals,
H. C.; Stork, B.; Coolen, H. K. A. C.; McCreary, A. C.; Adolfs, T. J. P.;
Kruse, C. G. Bioorg Med Chem Lett 2005, 15, 4794.
[18] Chimenti, F.; Maccioni, E.; Secci, D.; Bolasco, A.;
Chimenti, P.; Granese, A.; Befani, O.; Turini, P.; Alcaro, S.; Ortuso,
F.; Cirilli, R.; La Torre, F.; Cardia, M. C.; Distinto, S. J. Med Chem
2
005, 48, 7113.
Acknowledgments. The authors are grateful to the Head, Department
of Chemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad for providing the laboratory facility. The authors are
also thankful to the Director, SAIF, Punjab University, Chandigarh,
India for spectral analysis of novel compounds.
[19] (a) Chimenti, F.; Bizzarri, B.; Manna, F.; Bolasco, A.; Secci,
D.; Chimenti, P.; Granese, A.; Rivanera, D.; Lilli, D.; Scaltrito, M. M.;
Brenciaglia, M. I. Bioorg Med Chem Lett 2005, 15, 603; (b) Goodell,
J. R.; Puig-Basagoiti, F.; Forshey, B. M.; Shi, P. Y.; Ferguson, D. M. J.
Med Chem 2006, 49, 2127; (c) Reddy, M. V. R.; Billa, V. K.; Pallela,
V. R.; Mallireddigari, M. R.; Boominathan, R.; Gabriel, J. L.; Reddy,
E. P. Bioorg Med Chem 2008, 16, 3907; (d)Amir, M.; Kumar, H.; Khan,
S. A. Bioorg Med Chem Lett 2008, 18, 918.
REFERENCES AND NOTES
[20] (a) Jovanovic, S. V.; Steenken, S.; Tosic, M.; Marjanovic, B.;
Simic, M. G. J. Am Chem Soc 1994, 116, 4846; (b) Bors, W.; Heller, W.;
Michel, C.; Stettmaier, K. In Handbook of Antioxidants; Adenas, E.;
Packer, L. Eds.; Marcel Dekker: New York, 1996; 409.
[
[
1] Yagisawa, M. Jpn J Med Mycol 2004, 45, 77.
2] Johnson, E. M.; Szekely, A.; Warnock, D. W. Antimicrob
[21] Lombardino, J. G.; Otterness, I. G. J Med Chem 1977,
Agents Chemother 1999, 43, 1260.
3] Tsukuda, Y.; Shiratori, M.; Watanabe, H.; Ontsuka, H.;
Hattori, K.; Shirai, M.; Shimma, N. Bioorg Med Chem Lett 1998, 8, 1819.
4] Narayanan, A.; Chapman, D. R.; Upadhyaya, S. P.; Bauer, L. J
Heterocycl Chem 1993, 30, 1405.
5] Krakovsky, E. M. D. J.; Rybak, M. J. Pharmacotherapy 1990,
0, 146.
6] Roberts, J.; Schock, K.; Marino, S.; Andriole, V. T.
Antimicrob Agents Chemother 2000, 44, 3381.
7] Sanati, H.; Belanger, P.; Fratti, R.; Ghannoum, M. Antimicrob
Agents Chemother 1997, 41, 2492.
8] Richardson, K.; Bell, A. S.; Dickinson, R. P.; Naryanaswami,
S.; Hay, S. J.; Abstr. 35th Intersci. Conf. Antimicrob. Agents Chemother
995, F69, 125.
2
2
2
2
0, 830.
[
[22] Holla, B. S.; Akberali, P. M.; Shivananda, M. K. Il Farmaco
000, 55, 256.
[
[23] Flora, F. B.; Hanaa, M. H.; Adel, S. G. Bioorg Med Chem
006, 14, 3929
[
[24] Bansal, E.; Srivatsava, V. K.; Kumar, A. Eur J Med Chem
1
001, 36, 81.
[
[
25] Rathish, I. G.; Javed, K.; Ahmad, S.; Bano, S.; Alam, M. S.;
Pillai, K. K.; Singh, S.; Bagchi, V. Bioorg Med Chem Lett 2009,
9, 255.
26] Joshi, R. S.; Mandhane, P. G.; Diwakar, S. D.; Dabhade,
S. K.; Gill, C. H. Bioorg Med Chem Letts 2010, 20, 3721.
27] Jadhav, G. R.; Shaikh, M. U.; Kale, R. P.; Shiradkar. M.; Gill,
C. H. Eur J Med Chem 2009, 449, 2930.
28] Diwakar, S. D.; Bhagwat, S. S.; Shingare, M. S., Gill, C. H.
Bioorg Med Chem Letts 2008, 18, 4678.
29] Jadhav, G. R.; Shaikh, M. U.; Shingare, M. S.; Gill, C. H. J Het
Chem 2008, 45, 1287.
30] Jadhav, G. R.; Shaikh, M. U., Kale, R. P.; Ghawalkar, A. R.;
Nagargoje, D. R.; Shiradkar, M.; Gill, C. H. Bioorg Med Chem Lett
008, 16, 6244.
31] Godkar, P. B. In Text Book of Medical Laboratory
Technology, Bhalani Publishing House: Bombay, India, 1996.
32] Kilic, A.; Baysallar, M.; Besirbellioglu, B.; Salih, B.; Sorkun, K.;
Tanyuksel, M. Annals of Microbiol 2005, 55, 113.
[
1
[
[
[
1
[9] Espinel-Ingroff, A. J Clin Microbiol 1998, 36, 198.
[
[10] Boyle, F. T.; Gilman, D. J.; Gravestock, M. B.; Wardleworth,
J. M. Ann N Y Acad Sci 1988, 86, 544.
11] Pfaller, M. A.; Messer, S.; Jones, R. N. Antimicrob Agents
Chemother 1997, 41, 1124.
12] Bossche, H. V.; Marichal, P.; Le Jeune, L.; Coene, M. C.;
Gorrens, J.; Cools, W. Antimicrob Agents Chemother 1993, 37, 2101.
13] Massa, S.; Disanto, R.; Retico, A.; Artico, M.; Simmonetti, N.;
Fabrizi, G.; Lamba, D. Eur J Med Chem 1992, 27, 495.
[
[
[
[
2
[
[
[
[
14] Doignon, F.; Rozes, F. Lett Appl Microbiol 1992, 15, 172.
15] Tiboni, G. M. Res Commun Chem Pathol Pharmacol
[
1
993, 79, 381.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet