Synthesis and antifungal activity of some new 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones

Article abstract of DOI:10.1016/j.ejmech.2007.04.004

Seven new 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones 4a-g have been synthesized by the oxidation of 2-hydroxychalcone analogues of pyrazole 3a-g with hydrogen peroxide (H₂O₂) in KOH-MeOH by Algar Flynn Oymanda (AFO) reaction

Full text of DOI:10.1016/j.ejmech.2007.04.004

Available online at www.sciencedirect.com
European Journal of Medicinal Chemistry 43 (2008) 435e440
http://www.elsevier.com/locate/ejmech
Preliminary communication
Synthesis and antifungal activity of some new
3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones
a
b
Om Prakash a, , Rajesh Kumar , Vipin Parkash
*
a Department of Chemistry, Kurukshetra University, Kurukshetra 136119 Haryana, India
b Department of Botany, Kurukshetra University, Kurukshetra 136119 Haryana, India
Received 30 September 2006; received in revised form 2 April 2007; accepted 2 April 2007
Available online 29 April 2007
Abstract
Seven new 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones 4aeg have been synthesized by the oxidation of 2-hydroxychalcone ana-
logues of pyrazole 3aeg with hydrogen peroxide (H2O2) in KOHeMeOH by Algar Flynn Oymanda (AFO) reaction. The structures of the com-
1
pounds 4 were established by the combined use of H NMR, IR and mass spectra. All the seven compounds were tested in vitro for their
antifungal activity against three phytopathogenic fungi, namely Helminthosporium species, Fusarium oxysporum and Alternaria alternata.
Five compounds 4a, 4b, 4c, 4e and 4f were associated with substantially higher antifungal activity than commercial antifungal compound
Actidione (cycloheximide) against all three phytopathogenic fungi.
Ó 2007 Elsevier Masson SAS. All rights reserved.
Keywords: 3-Hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones; 2-Hydroxychalcone analogues of pyrazole; NMR; IR spectroscopy; Antifungal activity
1. Introduction
has been a particular interest in the synthesis of flavonols with
a wide array of groups at C-2. In view of these observations, it
was envisaged in the present investigation to undertake the
synthesis of a number of flavonols, having the pyrazole moiety
at position C-2 with an aim to find new and more potent
antifungal agents. We have synthesized some new 3-hydroxy-
2-(1-phenyl-3-aryl-4-pyrazolyl) chromones 4 as potential
antifungal agents by the oxidation of 2-hydroxychalcone
analogues of pyrazole 3 with hydrogen peroxide (H2O2) in
KOHeMeOH by AFO reaction. The synthesized compounds
4aeg were screened in vitro for their antifungal activity
against three phytopathogenic fungi, namely Helminthospo-
rium sp., Fusarium oxysporum and Alternaria alternata by
Poisoned Food Technique.
Flavonols are simply flavones in which a hydroxyl group
substitutes the 3-position, and have considerable physiologi-
cal, phylogenetic, chemosystematic, pharmacological, biosyn-
thetic and analytical significance. They display many diverse
types of biological properties such as antiproliferative [1,2],
antiviral [3e5], antioxidant [6,7], antifungal [8e10] and anti-
inflammatory [11]. They are also known to possess a good
synthetic application; especially photooxygenation [12],
superoxide anion [13] and reagents catalysed oxygenation re-
actions [14e19], which were non-enzymatic model reactions
for the biological oxygenation of flavonols. On the other
hand, substituted pyrazole ring also exhibits a broad spectrum
of biological activities such as antidiabetic [20], antibacterial
[21e23], antimicrobial [24e27] and herbicidal [28,29]. There
2. Chemistry
Synthesis of 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)
chromones 4 is outlined in Scheme 1. Thus, oxidation of 2-hy-
droxychalcone analogues of pyrazole 3 with hydrogen perox-
ide (H2O2) in KOHeMeOH might afford the desired products
Abbrevations: AFO, Algar Flynn Oymanda reaction; MeOH, methanol;
ppm, parts per million; PDA, potato dextrose agar.
* Corresponding author. Fax: þ91 1744238277.
E-mail address: dromprakash50@rediffmail.com (O. Prakash).
0223-5234/$ - see front matter Ó 2007 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2007.04.004

436
O. Prakash et al. / European Journal of Medicinal Chemistry 43 (2008) 435e440
Ar CHO
Ar
OH
OH
N
KOH
MeOH
+
N
CH3
N
Ph
N
Ph
2
O
O
3
1
KOH
MeOH
H2O2
Ar
Phenyl
3,4
a
Ar
N
b
c
4-methylphenyl
4-methoxyphenyl
4-chlorophenyl
4-bromophenyl
N
O
O
Ph
d
e
OH
4-fluorophenyl
4-nitrophenyl
f
4
g
Scheme 1.
3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones 4 in
high yields [30,31].
Helminthosporium sp. (58.6) and A. alternata (50.9) while
the growth of F. oxysporum (16) was inhibited in less extent.
Compound 4e displayed almost same inhibition against all
three phytopathogenic fungi at all concentrations. Compound
4d did not show any percentage inhibition on the growth of
F. oxysporum.
Accordingly, a solution of 2-hydroxychalcone 3a in KOHe
MeOH was treated with hydrogen peroxide by stirring at 0e
5 ꢀC for about 4e5 h. Usual work-up of the reaction afforded
the pure crystalline product 4a in 61% yield. Encouraged by
the feasibility of our strategy for 4a, we studied oxidative cy-
clization of a wide range of substituted 2-hydroxychalcones
3beg with hydrogen peroxide under similar conditions. The
2-hydroxychalcone analogues of pyrazole 3 were obtained
by the condensation of 2-hydroxyacetophenone 1 with 1-phe-
nyl-3-arylpyrazole-4-carboxaldehydes 2 in KOHeMeOH [32].
The structures of all the new 3-hydroxy-2-(1-phenyl-3-aryl-4-
pyrazolyl) chromones 4 and 2-hydroxychalcone analogues of
pyrazole 3 were confirmed by their spectral data (IR, 1H
NMR and MS ) and elemental analysis.
A careful analysis of percentage inhibition data revealed
some interesting trends (Table 1 and Fig. 1). (i) The compounds
4aeg inhibited the growth of phytopathogenic fungi signifi-
cantly at different concentrations. The inhibitory effects of
the compounds 4aeg were directly correlated with concentra-
tions. Hence, as concentration of the compounds 4aeg
increased (100e1000 ppm), the inhibition against all three phy-
topathogenic fungi also increased. The fungi are completely
inhibited at higher level of concentrations (<1000 ppm).
(ii) Comparison of the inhibition data of compounds 4aeg
suggested that by replacement of proton of aryl ring of pyrazole
moiety (at 3-position) in 3-hydroxy-2-(1-phenyl-3-aryl-4-pyra-
zolyl) chromones 4aeg with electron releasing groups the
antifungal activity increased while as the aryl proton is replaced
with electron withdrawing group the antifungal activity
decreased. The most striking examples in compounds 4aeg
are 4c and 4g compared with the parent compound 4a. In com-
pound 4c the aryl proton is replaced with methoxy group which
exhibited significant level of antifungal activity against all three
fungi while in compound 4g the aryl proton replaced with nitro
group which is almost inactive towards all three fungi.
3. Biological results and discussion
All the seven compounds were tested in vitro for their an-
tifungal activity against three phytopathogenic fungi, namely
Helminthosporium sp., F. oxysporum and A. alternata (Table 1
and Fig. 1). Five of these compounds 4a, 4b, 4c, 4e and 4f ex-
hibited good antifungal activity than commercial antifungal
compound Actidione (cycloheximide) against all three phyto-
pathogenic fungi. Compound 4c showed maximum inhibition
against Helminthosporium sp. (77.0), F. oxysporum (64.2) and
A. alternata (77.3) at 1000 ppm. Compound 4b was found
more effective against Helminthosporium sp. (76.1). It also in-
hibited the growth of F. oxysporum (55.7) and A. alternata
(61.8) at 1000 ppm. Compound 4a also inhibited the growth
of Helminthosporium sp. (71.2), F. oxysporum (51.7) and
A. alternata (52.8). Compound 4f inhibited the growth of
4. Conclusion
Using easily obtainable compounds 1 and 2 we have pre-
pared a new series of 2-hydroxychalcone analogues of pyra-
zole 3 and 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones

O. Prakash et al. / European Journal of Medicinal Chemistry 43 (2008) 435e440
437
Table 1
In vitro antifungal activity of 4aeg using Poisoned Food Technique
4 in good yields. Many of these compounds 4a, 4b, 4c, 4e and
4f showed excellent activity as displayed in Table 1 and Fig. 1.
The effect of presence of substituents such as methoxy and
nitro in the aryl ring of pyrazole moiety of compounds 4 on
antifungal activity has been shown.
Compounds Concentrations % Inhibition of phytopathogenic fungia
(in ppm)
Hs
Fo
Aa
4a
Control
100
500
0 ꢁ 0.12
0 ꢁ 0.05
0 ꢁ 0.11
31.0 ꢁ 0.04
50.5 ꢁ 0.32
71.2 ꢁ 0.39
33.9 ꢁ 0.12
39.2 ꢁ 0.18
51.7 ꢁ 0.10
15.0 ꢁ 0.55
41.5 ꢁ 0.36
52.8 ꢁ 0.44
1000
5. Experimental
4b
Control
100
500
0 ꢁ 0.05
73.8 ꢁ 0.07
73.8 ꢁ 0.07
76.1 ꢁ 0.04
0 ꢁ 0.11
50.0 ꢁ 0.07
51.4 ꢁ 0.07
55.7 ꢁ 0.05
0 ꢁ 0.04
60.0 ꢁ 0.05
61.8 ꢁ 0.05
61.8 ꢁ 0.05
Melting points were determined in open capillaries with
electrical melting point apparatus and are uncorrected. The
IR spectra were obtained with a Buck Scientific IR M-500
1000
1
4c
Control
100
500
0 ꢁ 0.12
59.7 ꢁ 0.03
59.7 ꢁ 0.04
77.6 ꢁ 0.05
0 ꢁ 0.05
55.5 ꢁ 0.04
55.3 ꢁ 0.07
64.2 ꢁ 0.05
0 ꢁ 0.11
0 ꢁ 0.04
0 ꢁ 0.04
0 ꢁ 0.04
0 ꢁ 0.11
73.5 ꢁ 0.10
75.4 ꢁ 0.05
77.3 ꢁ 0.09
spectrophotometer. The H NMR spectra were recorded on
a Bruker (300 MHz) spectrometer using tetramethylsilane as
an internal standard. All the new compounds gave satisfactory
analytical results (within ꢁ0.4 of the theoretical values).
1-Phenyl-3-arylpyrazole-4-carboxaldehydes 2aeg needed
in this study were prepared by VilsmeiereHaack reaction of
acetophenone phenylhydrazones [33].
1000
4d
Control
100
500
0 ꢁ 0.05
0 ꢁ 0.04
0 ꢁ 0.05
0 ꢁ 0.04
1.19 ꢁ 0.05
21.4 ꢁ 0.43
38.2 ꢁ 0.13
38.2 ꢁ 0.13
1000
4e
Control
100
500
0 ꢁ 0.05
39.0 ꢁ 0.11
39.2 ꢁ 0.23
39.2 ꢁ 0.23
0 ꢁ 0.11
34.2 ꢁ 0.11
35.7 ꢁ 0.04
41.4 ꢁ 0.05
0 ꢁ 0.04
25.4 ꢁ 0.05
29.0 ꢁ 0.05
34.5 ꢁ 0.05
5.1. 2-Hydroxychalcone analogues of pyrazole (3aeg)
1000
4f
Control
100
500
0 ꢁ 0.12
12.3 ꢁ 0.10
28.7 ꢁ 0.27
58.6 ꢁ 0.32
0 ꢁ 0.25
1.31 ꢁ 0.25
1.31 ꢁ 0.25
14.4 ꢁ 0.25
0 ꢁ 0.005
38.5 ꢁ 0.07
41.5 ꢁ 0.02
50.0 ꢁ 0.05
0 ꢁ 0.05
8.9 ꢁ 0.20
8.9 ꢁ 0.05
16.0 ꢁ 0.12
0 ꢁ 0.35
8.57 ꢁ 0.10
11.4 ꢁ 0.35
14.2 ꢁ 1.11
0 ꢁ 0.11
39.2 ꢁ 0.13
43.4 ꢁ 0.05
50.2 ꢁ 0.06
0 ꢁ 0.11
30.1 ꢁ 0.27
43.3 ꢁ 0.17
50.9 ꢁ 0.10
To a solution of KOH (1.12 g, 0.02 mol) in methanol
(50 ml) was added 2-hydroxyacetophenone
1 (1.36 g,
0.01 mol) and 1-phenyl-3-(4-methylphenyl) pyrazole-4-car-
boxaldehydes 2 (2.62 g, 0.01 mol) at 0e5 ꢀC. The reaction
mixture was stirred overnight at room temperature. Then,
this reaction mixture was poured over crushed ice and acidi-
fied with dil. HCl. The yellow solid thus obtained was filtered,
washed with water and dried. The crude product was crystal-
lized with chloroformeethanol to afford pure 2-hydroxychal-
cones 3aeg.
1000
4g
Control
100
500
0 ꢁ 0.0
0 ꢁ 0.0
16.1 ꢁ 0.35
16.1 ꢁ 0.35
1000
Ac (Cy)
Control
100
500
0 ꢁ 0.04
40.2 ꢁ 0.05
45.5 ꢁ 0.12
50.6 ꢁ 0.10
1000
The physical, analytical and spectral data of new 2-hydrox-
ychalcone analogues of pyrazole 3 are given below.
Ac, Actidione; Cy, cycloheximide.
Mean of three replicates, ꢁstandard deviation.
a
Hs, Helminthosporium species; Fo, Fusarium oxysporum; Aa, Alternaria
alternata.
5.1.1. 1-(2-Hydroxyphenyl)-3-(1,3-diphenyl-4-pyrazolyl) prop-
2-en-1-one (3a)
Yield 64%; mp 162e163 ꢀC; IR (KBr): 1638 cmꢂ1 (C]O
1
str.); H NMR (CDCl3, 300 MHz): d 12.92 (s, 1H, OH), 8.41
(s, 1H), 7.40 (d, 1H, J ¼ 8.4 Hz), 7.04 (d, 1H, J ¼ 8.4 Hz),
8.03 (d, 1H, J ¼ 15.3 Hz), 6.93 (m, 1H), 7.49e7.56 (m, 7H),
7.73e7.85 (m, 5H). Anal. Cald. for C24H18N2O2: C, 78.69,
H, 4.92, N, 7.65. Found: C, 78.52, H, 4.93, N, 7.85.
80
70
60
50
40
30
20
10
0
Hs
Fo
Aa
5.1.2. 1-(2-Hydroxyphenyl)-3-[(1-phenyl-3-(4-methylphenyl)-
4-pyrazolyl)] prop-2-en-1-one (3b)
Yield 58%; mp 143e145 ꢀC; IR (KBr): 1638.6 cmꢂ1
(C]O str.); 1H NMR (CDCl3, 300 MHz): d 2.47 (s, 3H,
CH3), 12.94 (s, 1H, OH), 8.4 (s, 1H), 8.02 (d, 1H,
J ¼ 15.3 Hz), 7.63 (d, 2H, J ¼ 7.8 Hz), 7.35 (d, 2H,
J ¼ 7.8 Hz), 7.09 (d, 1H, J ¼ 8.4 Hz), 7.40 (d, 1H,
J ¼ 8.4 Hz), 6.93 (m, 1H), 7.48e7.55 (m, 4H), 7.79e7.84
(m, 3H). Anal. Cald. for C25H20N2O2: C, 78.95, H, 5.26, N,
7.37. Found: C, 78.60, H, 5.41, N, 7.51.
4a
4b
4c
4d
Compounds
4e
4f
4g
Fig. 1. Comparison of antifungal activity of compounds 4aeg against three
fungi at concentration 1000 ppm.

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O. Prakash et al. / European Journal of Medicinal Chemistry 43 (2008) 435e440
5.1.3. 1-(2-Hydroxyphenyl)-3-[(1-phenyl-3-(4-methoxyphenyl)-
4-pyrazolyl)] prop-2-en-1-one (3c)
KOH (10 ml, 20%), cooled at 5e10 ꢀC, was added 30%
H2O2 (10 ml) dropwise over 1 h. The reaction mixture was fur-
ther stirred for 4e5 h. The resulting light yellow reaction mix-
ture was poured on crushed ice and neutralized with dil. HCl.
The light yellow solid thus obtained was filtered, washed with
water and dried. The crude product was crystallized with
chloroformeethanol to afford pure 3-hydroxy-2-(1-phenyl-3-
aryl-4-pyrazolyl) chromones 4.
Yield 54%; mp 150e152 ꢀC; IR (KBr): 1638 cmꢂ1 (C]O
str.); 1H NMR (CDCl3, 300 MHz): d 3.91 (s, 3H, OCH3),
12.94 (s, 1H, OH), 8.4 (s, 1H), 7.04 (d, 1H, J ¼ 8.4 Hz),
7.39 (d, 1H, J ¼ 8.4 Hz), 7.67 (d, 2H, J ¼ 8.7 Hz), 7.08 (d,
2H, J ¼ 8.7 Hz), 6.94 (m, 1H), 8,02 (d, 1H, J ¼ 15.3 Hz),
7.82e7.84 (m, 3H), 7.48e7.55 (m, 4H). Anal. Cald. for
C25H20N2O3: C, 75.76, H, 5.05, N, 7.07. Found: C, 75.28,
H, 4.92, N, 6.96.
The physical, analytical and spectral data of 3-hydroxy-2-
(1-phenyl-3-aryl-4-pyrazolyl) chromones 4aeg are given
below.
5.1.4. 1-(2-Hydroxyphenyl)-3-[(1-phenyl-3-(4-chlorophenyl)-
4-pyrazolyl)] prop-2-en-1-one (3d)
5.2.1. 3-Hydroxy-2-(1,3-diphenyl-4-pyrazolyl) chromone (4a)
Yield 61%; mp 209e210 ꢀC; IR (KBr): 3306 cmꢂ1 (eOH
Yield 62%; mp 165e166 ꢀC; IR (KBr): 1639.2 cmꢂ1 (C]O
str.); 1H NMR (CDCl3, 300 MHz): d 12.88 (s, 1H, OH), 8.40 (s,
1H), 7.97 (d, 1H, J ¼ 15.3 Hz), 7.41 (d, 1H, J ¼ 8.4 Hz), 7.04 (d,
1H, J ¼ 8.4 Hz), 7.68 (d, 2H, J ¼ 8.4 Hz), 7.48 (d, 2H,
J ¼ 8.4 Hz), 6.95 (m, 1H), 7.50e7.56 (m, 4H), 7.80e7.83 (m,
3H). Anal. Cald. for C24H17N2O2Cl: C, 71.82, H, 4.24, N,
6.98. Found: C, 71.29, H, 4.36, N, 7.15.
1
str.), 1609 cmꢂ1 (C]O str.); H NMR (CDCl3, 300 MHz):
d 8.86 (s, 1H), 8.24 (dd, 1H, J ¼ 1.5, 8.1 Hz), 7.88 (d, 2H,
J ¼ 7.5 Hz), 7.71e7.74 (m, 2H), 7.49e7.59 (m, 6H), 7.36e
7.41 (m, 2H), 6.90 (d, 1H, J ¼ 8.4 Hz). Anal. Cald. for
C24H16N2O3: C, 75.79, H, 4.21, N, 7.36. Found: C, 74.95,
H, 4.08, N, 7.51; MS: m/z, Mþ 380.
5.1.5. 1-(2-Hydroxyphenyl)-3-[(1-phenyl-3-(4-bromophenyl)-
4-pyrazolyl)] prop-2-en-1-one (3e)
5.2.2. 3-Hydroxy-2-[(1-phenyl-3-(4-methylphenyl)-4-pyrazolyl)]
chromone (4b)
Yield 51%; mp 171e173 ꢀC; IR (KBr): 1638.2 cmꢂ1
Yield 58%; mp 221e224 ꢀC; IR (KBr): 3284 cmꢂ1 (eOH
1
(C]O str.); H NMR (CDCl3, 300 MHz): d 12.87 (s, 1H,
1
str.), 1611 cmꢂ1 (C]O str.); H NMR (CDCl3, 300 MHz):
OH), 8.41 (s, 1H), 7.42 (d, 1H, J ¼ 8.4 Hz), 7.05 (d, 1H,
J ¼ 8.4 Hz), 7.69 (d, 2H, J ¼ 8.1 Hz), 7.63 (d, 2H,
J ¼ 8.1 Hz), 6.95 (m, 1H), 7.48e7.56 (m, 4H), 7.80e7.84
(m, 3H), 7.93 (d, 1H, J ¼ 15.3 Hz). Anal. Cald. for
C24H17N2O2Br: C, 64.72, H, 3.82, N, 6.29. Found: C, 64.19,
H, 3.80, N, 6.42.
d 2.49 (s, 3H, CH3), 8.86 (s, 1H), 8.25 (dd, 1H, J ¼ 1.5,
7.8 Hz), 7.87 (d, 2H, J ¼ 7.8 Hz), 7.30 (d, 2H, J ¼ 7.8 Hz),
6.97 (d, 1H, J ¼ 8.4 Hz), 7.53e7.63 (m, 5H), 7.36e7.40 (m,
2H). Anal. Cald. for C25H18N2O3:, C, 76.14, H, 4.57, N,
7.11. Found: C, 75.88, H, 4.73, N, 7.24; MS: m/z, Mþ 394.
5.2.3. 3-Hydroxy-2-[(1-phenyl-3-(4-methoxyphenyl)-4-
pyrazolyl)] chromone (4c)
5.1.6. 1-(2-Hydroxyphenyl)-3-[(1-phenyl-3-(4-fluorophenyl)-
4-pyrazolyl)] prop-2-en-1-one (3f)
Yield 52%; mp 202e204 ꢀC; IR (KBr): 3298 cmꢂ1 (eOH
1
Yield 61%; mp 184e186 ꢀC; IR (KBr): 1638 cmꢂ1 (C]O
str.), 1611 cmꢂ1 (C]O str.); H NMR (CDCl3, 300 MHz):
1
str.); H NMR (CDCl3, 300 MHz): d 12.87 (s, 1H, OH), 8.40
d 3.93 (s, 3H, CH3), 8.85 (s, 1H), 8.25 (dd, 1H, J ¼ 1.5,
8.1 Hz), 7.87 (d, 2H, J ¼ 7.8 Hz), 7.67 (d, 2H, J ¼ 8.7 Hz),
7.03 (d, 2H, J ¼ 8.7 Hz), 7.50e7.57 (m, 4H), 7.36e7.40 (m,
2H). Anal. Cald. for C25H18N2O4: C, 73.17, H, 4.39, N,
6.83. Found: C, 73.35, H, 4.38, N, 6.88; MS: m/z, Mþ 410.
(s, 1H), 7.69 (d, 2H, J ¼ 8.4 Hz), 7.61 (d, 2H, J ¼ 8.4 Hz),
7.55 (d, 1H, J ¼ 8.4 Hz), 7.05 (d, 1H, J ¼ 8.4 Hz), 6.92e
6.97 (m, 1H), 7.47e7.52 (m, 3H), 7.79e7.83 (m, 3H), 7.97
(d, 1H, J ¼ 15.3 Hz), 7.37e7.41 (m, 1H). Anal. Cald. for
C24H17N2O2F: C, 75.00, H, 4.43, N, 7.29. Found: C, 74.89,
H, 4.35, N, 6.99.
5.2.4. 3-Hydroxy-2-[(1-phenyl-3-(4-chlorophenyl)-4-
pyrazolyl)] chromone (4d)
5.1.7. 1-(2-Hydroxyphenyl)-3-[(1-phenyl-3-(4-nitrophenyl)-
4-pyrazolyl)] prop-2-en-1-one (3g)
Yield 61%; mp 244e246 ꢀC; IR (KBr): 3278 cmꢂ1 (eOH
1
str.), 1613 cmꢂ1 (C]O str.); H NMR (CDCl3, 300 MHz):
Yield 64%; mp 195e197 ꢀC; IR (KBr): 1640 cmꢂ1 (C]O
d 8.86 (s, 1H), 8.25 (dd, 1H, J ¼ 1.5, 8.1 Hz), 7.85 (d, 2H,
J ¼ 8.4 Hz), 7.67 (d, 2H, J ¼ 8.4 Hz), 7.40e7.51 (m, 7H),
6.98 (d, 1H, J ¼ 8.4 Hz). Anal. Cald. for C24H15N2O3Cl: C,
69.40, H, 3.61, N, 6.75. Found: C, 69.62, H, 3.68, N, 6.62;
MS: m/z, Mþ 414.
1
str.); H NMR (CDCl3, 300 MHz): d 12.86 (s, 1H, OH), 8.31
(d, 2H, J ¼ 9.0 Hz), 8.05 (d, 2H, J ¼ 9.0 Hz), 8.41 (s, 1H),
7.96 (d, 1H, J ¼ 15.3 Hz), 6.95 (m, 1H), 7.47e7.57 (m, 5H),
7.73e7.85 (m, 4H). Anal. Cald. for C24H17N3O4: C, 70.07,
H, 4.14, N, 10.22. Found: C, 69.78, H, 4.04, N, 9.92.
5.2.5. 3-Hydroxy-2-[(1-phenyl-3-(4-bromophenyl)-4-
pyrazolyl)] chromone (4e)
5.2. 3-Hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)
chromones (4aeg)
Yield 52%; mp 232e234 ꢀC; IR (KBr): 3280 cmꢂ1 (eOH
1
str.), 1612 cmꢂ1 (C]O str.); H NMR (CDCl3, 300 MHz):
General procedure. To a well-stirred solution of 2-hydrox-
ychalcones 3 (2.0 g, 0.007 mol) in MeOH (20 ml) and aq.
d 8.86 (s, 1H), 8.26 (dd, 1H, J ¼ 1.5, 8.1 Hz), 7.86 (d, 2H,
J ¼ 7.8 Hz), 7.55 (d, 2H, J ¼ 7.8 Hz), 7.39e7.47 (m, 3H),

O. Prakash et al. / European Journal of Medicinal Chemistry 43 (2008) 435e440
439
7.62e7.72 (m, 4H), 6.99 (d, 1H, J ¼ 8.4 Hz). Anal. Cald. for
C24H15N2O3Br: C, 62.75, H, 3.27, N, 6.10. Found: C, 62.93,
H, 3.22, N, 6.04; MS: m/z, Mþ 459.
in each was determined by measuring radial mycelial growth.
The radial growth of the colony was measured in two direc-
tions at right angles to each other, and the average of three rep-
licates was recorded in each case. Data were expressed as
percent inhibition over control from the size of the colonies,
and subjected to two-way analysis of variance (ANOVA).
The percentage inhibition given in Table 1 was calculated
using the formula [36]:
5.2.6. 3-Hydroxy-2-[(1-phenyl-3-(4-fluorophenyl)-4-
pyrazolyl)] chromone (4f)
Yield 58%; mp 226e228 ꢀC; IR (KBr): 3300 cmꢂ1 (eOH
1
str.), 1610 cmꢂ1 (C]O str.); H NMR (CDCl3, 300 MHz):
d 8.86 (s, 1H), 8.24 (dd, 1H, J ¼ 1.5, 8.1 Hz), 7.51e7.91 (m,
9H), 7.06e7.22 (m, 3H). Anal. Cald. for C24H15N2O3F: C,
72.36, H, 3.77, N, 7.04. Found: C, 72.30, H, 3.70, N, 6.9;
MS: m/z, Mþ 398.
Percentage inhibition ¼ ðC ꢂ TÞ ꢃ 100=C
where C ¼ diameter of the fungus colony in the control
plate after 96 h;
T ¼ diameter of the fungus colony in tested plates after the
same period.
5.2.7. 3-Hydroxy-2-[(1-phenyl-3-(4-nitrophenyl)-4-
pyrazolyl)] chromone (4g)
Yield 57%; mp 237e239 ꢀC; IR (KBr): 3297 cmꢂ1 (eOH
1
str.), 1609 cmꢂ1 (C]O str.); H NMR (CDCl3, 300 MHz):
Acknowledgements
d 8.82 (s, 1H), 8.20 (dd, 1H, J ¼ 1.5, 8.1 Hz), 8.37 (d, 2H,
J ¼ 8.4 Hz), 8.13 (d, 2H, J ¼ 8.4 Hz), 7.45e7.59 (m, 6H),
7.06e7.18 (m, 2H). Anal. Cald. for C24H15N3O5: C, 67.76,
H, 3.53, N, 9.88. Found: C, 67.62, H, 3.32, N, 9.51; MS: m/
z, Mþ 425.
We are thankful to CSIR, New Delhi for the award of Se-
nior Research Fellowship to Rajesh Kumar. Thanks are also
due to RSIC, CDRI, Lucknow, India, for providing mass and
elemental analyses.
6. In vitro biological assay
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