Synthesis and antibacterial and antifungal evaluation of some chalcone based sulfones and bisulfones

Article abstract of DOI:10.1016/j.ejmech.2012.09.004

Two series of chalcone based sulfone and bisulfone derivatives were synthesized using chalcone, thiophenol and sodium metal at room temperature, followed by oxidation of chalcone sulfides with m-CPBA at 0 °C in a novel method. Both sulfones and bisulfones

Full text of DOI:10.1016/j.ejmech.2012.09.004

European Journal of Medicinal Chemistry 59 (2013) 23e30
Contents lists available at SciVerse ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Short communication
Synthesis and antibacterial and antifungal evaluation of some chalcone based
sulfones and bisulfones
,
Naveen Kumar Konduru a, Sunita Dey a, Mohammad Sajid b, Mohammad Owais b, Naseem Ahmed a
*
a Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India
b Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Two series of chalcone based sulfone and bisulfone derivatives were synthesized using chalcone, thio-
phenol and sodium metal at room temperature, followed by oxidation of chalcone sulfides with m-CPBA
at 0 ꢀC in a novel method. Both sulfones and bisulfones were evaluated for their antimicrobial activities
against Aspergillus niger and Candida albicans (yeast), Bacillus subtilis and Staphylococcus aureus (Gram
(þ) bacteria) and Pseudomonas aeruginosa and Salmonella typhimurium (Gram (ꢁ) bacteria) strains.
Among them, compounds 2c, 3c, 6c, 7c, 8c and 9c have shown high antifungal activity against C. albicans
compare to reference drugs viz. Amphotericin-B and Nystatin. Compound 1c has shown slightly better
antibacterial activity against B. subtilis and compounds 5c, 6c and 7c have shown excellent antibacterial
activity against S. typhimurium in compare to reference drugs Ampicillin and Kanamycin.
Ó 2012 Elsevier Masson SAS. All rights reserved.
Received 15 April 2012
Received in revised form
31 August 2012
Accepted 3 September 2012
Available online 10 September 2012
Keywords:
Chalcone sulfones & bisulfones
m-CPBA
Antibacterial and antifungal activities
1. Introduction
stoichiometric or catalytic amounts of inorganic reagents [14e22].
However, oxidation of sulfides using these reagents is slow and
Sulfones have entertained a special status as a versatile building
blocks in the synthesis of biologically active compounds, fine
chemicals and chiral auxiliaries [1,2]. Many sulfone derivatives have
been exploited in synthetic organic and medicinal chemistry [3].
Sulfone containing molecules widely used as antinociceptive and
anti-inflammatory drugs. Chemically, sulfonyl group is well-
established as activating moiety in a number of intermediates for
the construction of CeC and Ceheteroatoms bond formation
during organic transformations [4e8]. Recently, they have been
used in total syntheses and in the generation of database of func-
tionalized compounds. Also, these moieties have potential to
stabilize carbanions and radicals and act as cationic reagents [9e
11]. Similarly, sulfone groups facilitate conjugate addition by acti-
vation of the olefins with Lewis acids [12]. Moreover, removal of
sulfonyl groups might be possible by a reductive process or via
gives a mixture of compounds due to their rapid decomposition
[23e25]. Therefore, extensive studies have been undertaken to
develop new catalysts for such reactions. Previously, formation of
chalcone based sulfones was reported in the literature although
they have limitations due to poor yields, longer reaction time and
need of catalysts or additives for better yields [12]. In the present
study, m-CPBA has been used as oxidant first time at room
temperature which converted quantitatively sulfides to sulfones
under simple reaction condition.
2. Results and discussion
2.1. Chemistry
Chalcones were prepared following literature procedures by the
condensation of acetophenones with aromatic aldehydes [26,27].
The corresponding chalcone based sulfides were synthesized by the
reaction of chalcones, thiophenol and sodium metal in DCM at room
temperature via Thia-Michael addition reaction (Schemes 1 and 2)
[28]. Further, the corresponding sulfones were prepared in good
yields using m-CPBA as oxidizing agent in DCM at 0 ꢀC to room
temperature (Schemes 1 and 2, Tables 2 and 3).
a base-promoted b-elimination route [13].
Synthesis of sulfones is mainly reported via oxidation of the
corresponding sulfides, which is typically achieved using
Abbreviations: m-CPBA, meta-chloroperbenzoic acid; DCM, dichloromethane;
m
g, microgram; ml, microliter; mM, micromole; ml, milliliter; mg, milligram; mmol,
millimole; nm, nanometer; DMSO, dimethyl sulfoxide; DPPH, 2,2-diphenyl-1-
picrylhydrazyl.
We also tried hydrogen peroxide as an oxidant under different
reaction conditions like 0 ꢀC, room temperature and at reflux with
varying solvents (AcOH, THF, MeCN) which gave decomposed
* Corresponding author. Tel./fax: þ91 1332 285745.
E-mail address: nasemfcy@iitr.ernet.in (N. Ahmed).
0223-5234/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.ejmech.2012.09.004

24
N.K. Konduru et al. / European Journal of Medicinal Chemistry 59 (2013) 23e30
O
O
S
R4
R3
PhSH, Na, DCM
rt, 2.5-4 hr
R4
R3
R1
R1
R2
R2
m-CPBA
0
0C to rt
R1 = H, Cl, Br
4.5-6 h
R2 = H, OMe NO2;
R3 = H, Cl, OMe
R4 = H, OMe
O
S
O
O
R4
R3
R1
R2
Scheme 1. Synthesis of chalcone sulfones (1ce7c).
mixture of sulfoxide and sulfone along with about 50% reactant.
Further, changes in hydrogen peroxide concentrations have unfa-
vorable effects in the reaction due to rapid decomposition of
hydrogen peroxide. Then, m-CPBA is used as oxidant which easily
converted sulfides to sulfones under an optimized reaction condi-
tion (Table 1).
stretch.) at 1304 cmꢁ1 characterize the product and in comparison
with sulfide 1b, shifting of -value of protons in 1c from 4.57 to 4.96
and -value of carbons from 47.6 to 65.74 are indicating sulfide
converted to sulfone.
For 1,5-di(4-methylphenyl)-1,5-bis(phenylsulfonyl)pentan-3-one
8c, 1H NMR spectrum contained peak at
4.95 ppm (dd, J ¼ 9 Hz,
4.5 Hz, 2H), 3.64 (dd, J ¼ 17.5 Hz, 4.5 Hz, 2H), 3.17e3.12 ppm (m,
2H); 13C NMR spectrum
60.55 and 30.66 ppm and IR(assy. stretch.)
at 1302 cmꢁ1 characterize the product and in comparison with 8b,
shifting of -value of protons in 8c from 4.32 to 4.95 and -value of
d
d
d
Using above protocol, we have prepared sulfones 1ce7c and
bisulfones 8ce11c. Compounds 1ce7c were prepared using sulfide
and m-CPBA in 1:2.2 mmol ratio and compounds 8ce11c (Scheme
2) using sulfide and m-CPBA in 1:4.5 mmol ratio due to two SO2
groups which gave good yields without further purification. No
significant substituent effects were observed in sulfone formation
and excellent yields obtained in all cases (Tables 2 and 3). These
products were confirmed on the basis of their analytical data (1H,
13C, IR and elemental analysis) and physico-chemical properties
data like color, melting point and molecular weight (Table 4) and
also comparison with reported values in the literature [29]. For
example, 1,3-bis(4-chlorophenyl)-3-(phenylsulfonyl)propan-1-one
d
d
d
d
carbons from 49.51 to 60.55 are indicating sulfide converted to
sulfone.
2.2. In-vitro antimicrobial assay/studies
2.2.1. Microdilution assay
Minimum inhibitory concentration (MIC) is the lowest concen-
tration of an antimicrobial compound that inhibits the visible
growth of a microorganism. MIC values of the compounds against
bacterial and fungal isolates were determined on the basis of
micro-well dilution method following NCCLS recommendations
1c, 1H NMR spectrum contained peak at
d
4.96 ppm (dd, J ¼ 9.5 Hz,
3 Hz, 1H),
d
4.12 ppm (dd, J ¼ 18 Hz, 3.5 Hz, 1H),
d
3.86e3.80 ppm
(m, 1H); 13C NMR spectrum
d
65.74 and, 36.85 ppm and IR (assy.
O
S
O
S
PhSH
Na
rt, DCM
R1
R1
10-60 min
R1
R1
mCPBA
0 0C to rt
5-6 hr
R1 = H, Cl, Me, OMe
O
S
O
O
O O
S
R1
R1
Scheme 2. Synthesis of double chalcone sulfones (8ce11c).

N.K. Konduru et al. / European Journal of Medicinal Chemistry 59 (2013) 23e30
25
Table 1
Positive control contained only microbial cells where as negative
control contained only standard drug solution (Amphotericin-B,
Nystatin for fungus and Ampicillin, Kanamycin for bacteria). All
experimental procedures were performed under sterile condition
using bio-safety hood and microtitre plates were incubated at 37 ꢀC
for 12e18 h.
Optimization of reaction conditions.
Entry
Sulfide (mmol)
m-CPBA (mmol)
Yield (%)
Sulfoxide:sulfone
1.
2.
3.
4.
1
1
1
1
1
1.5
2
50
60
80
95
80:20
30:70
20:80
0:100
2.2
2.2.2. Antimicrobial activity
Synthesized compounds (1ce11c) were screened for their
antimicrobial activity. Two yeast (Aspergillus niger and Candida
albicans), two gram positive bacteria (Bacillus subtilis and Staphy-
lococcus aureus) and two gram negative bacteria (Pseudomonas
aeruginosa and Salmonella typhimurium) were selected to evaluate
the effectiveness of the test compounds (details in Experimental
section).
[30]. In this method we made stock of chemically synthesized
compounds at a concentration of 10 mg/ml in DMSO, which was
further converted to working solution of concentration 1 mg/ml
solution in methanol. Using a micropipette, 100 ml of media into all
wells of pre-sterilized microtitre plate was dispensed (experiment
was done in triplicate). Two fold serial dilutions were carried out
from the well 1 to the well 10 and excess media (100 ml) was dis-
carded from the last well (No. 10). Liquid culture of test organism
was grown to a suitable phase in corresponding medium (Yeast,
2.2.2.1. Antibacterial activity. Compounds 1ce11c was subjected to
MIC (minimum inhibitory concentration) determination by
microdilution method [31] and the results are given in Table 5.
Reference drugs Ampicillin and Kanamycin were chosen as positive
control in antibacterial activity assay.
Peptone, and D-Glucose for fungal growth and Luria Bertani Broth,
Nutrient Broth for bacterial growth) for 12e18 h at 37 ꢀC. Then
optical density of liquid culture was determined at 600 nm and
diluted in such a way that each well received 104 cfu/100
ml of
As seen in the Table 5, compounds 5c, 7c, 8c, 10c (MIC: 62.50 mg/
ml) have shown better antimicrobial activity than positive control
fungal suspension and 107 cfu/100
ml of bacterial culture. Appro-
priate positive and negative control was also included in the study.
against S. aureus. In case of B. subtilis, all compounds have shown
Table 2
Synthesis of sulfones (1ce7c) from chalcones.
S No.
Chalcone
Reaction time
Yield (%)
90
Michael adduct
Reaction time
5 h
Yield (%)
89
Sulfone
O
S
Ph
O
Ph
O
O
S
O
1.
4 h
1b
1a
1c
Cl
Cl
Cl
Cl
Cl
Cl
O
S
Ph
Ph
O
O
S
O
O
2.
3.
3 h
3 h
90
92
4.5 h
4.5 h
90
88
2a
Cl
Cl
Ph
2b
Cl
2c
O
S
O
O
S
Ph
O
O
O
NO2
3a
Cl
Cl
3b
NO
Cl
NO2
3c
O
S
Ph
Ph
O
O
O
S
S
O
4.
5.
3 h
3 h
95
95
5 h
5 h
92
86
Br
4a
4b
Br
Br
4c
Br
Br
O
S
Ph
Ph
O
O
O
Br
O
O
O
O
5b
5a
5c
O
O
O
O
S
O
Ph
Ph
O
O
S
O
O
O
O
6.
7.
3 h
89
95
6 h
80
93
Br
O
Br
O
Br
6a
O
6b
O
6c
O
O
S
Ph
O
O
Ph
O
S
O
2.5 h
4.5 h
7a
7b
7c

26
N.K. Konduru et al. / European Journal of Medicinal Chemistry 59 (2013) 23e30
Table 3
Synthesis of double sulfones (8ce11c) from double chalcones.
S No.
8.
Chalcone
Reaction time
Yield (%)
92
Michael adduct
Reaction time
5 h
Yield (%)
90
Sulfone
Ph
S
Ph
Ph
Ph
O
S
O
S
O
O O
O
S
O
10 min
Me
Cl
Me
Me
Cl
Me
Cl
8a
8b
Me
Cl
Me
8c
Ph
Ph
S
Ph
Ph
O
S
O
S
O
S
O O
O
O
9.
10 min
90
5.5 h
88
Cl
Cl
9a
9b
9c
Ph
S
Ph
S
Ph
Ph
O
S
O
S
O
O O O
O
10.
11.
10 min
60 min
90
89
5 h
6 h
89
80
10a
10b
10c
O
O
O
11a
lower activity than positive control (Kanamycin) while compound
1c (MIC: 15.62 g/ml) has shown better antibacterial activity
against B. subtilis. Moreover, compounds 6c, 7c, 9c, 11c (MIC:
31.25 g/ml) and compounds 2c, 3c, 4c, 5c, 8c (MIC: 62.50 g/ml)
have demonstrated sound activity against B. subtilis than Ampicillin
drug. Compounds 2c, 3c, 4c, 5c, 8c, 10c (MIC: 62.50 g/ml) have
shown better activity than positive controls against P. aeruginosa
while others have shown lower activity (MIC ꢂ 125 g/ml).
Compounds 5c, 6c, 7c have shown admirable antibacterial activity
(MIC: 1.95 g/ml) against S. typhimurium while 9c (MIC: 15.62 g/
ml), 8c (MIC: 31.25 g/ml) and 3c, 11c (MIC: 62.50 g/ml) have
on aromatic ring have shown less antibacterial activity (MIC:
250 g/mle62.50 g/ml) against S. typhimurium (compounds 1c, 2c,
3c, 4c, 11c). Against S. aureus also either electron releasing groups
(OMe or Me) or without substitution on aromatic ring have
shown good (MIC: 62.50 mg/ml) antibacterial activity (compounds
5c, 7c, 8c, 10c). Against B. subtilis, all compounds have shown low
activity compare to standard drug Kanamycin without depending
on functional groups on aromatic ring. While, compare to
standard drug Ampicillin against B. subtilis, trimethoxy group
containing compounds 6c, 11c have shown good antibacterial
m
m
m
m
m
m
m
m
m
m
m
activity (MIC: 31.25 mg/ml). Against P. aeruginosa compare to
shown comparable antibacterial activity against S. typhimurium as
compare to positive control Ampicillin. Thus, both electron
releasing groups (OMe or Me) and without substitution sulfones
standards (Kanamycin, Ampicillin) electron withdrawing groups
containing compounds 2c, 3c, 4c have shown good activity.
have shown excellent (MIC: 1.95
antibacterial activity against S. typhimurium (compounds 5c, 6c, 7c
and 8c). Sulfones having electron withdrawing groups (Cl, Br, NO2)
m
g/ml) to good (MIC: 31.25
m
g/ml)
2.2.2.2. Antifungal activity. Compounds 1ce11c was subjected to
MIC (minimum inhibitory concentration) determination by
microdilution method [31] and the results are given in Table 6.
Reference drugs Amphotericin-B and Nystatin were selected as
positive control in antifungal activity assay.
Table 4
Physico-chemical properties of synthesized compounds.
Compound
M.P. (ꢀC)
M.F.
M.W.
White solid (1b)
White solid (2b)
White solid (3b)
White solid (4b)
White solid (5b)
White solid (6b)
White solid (7b)
White solid (8b)
White solid (9b)
White solid (10b)
White solid (11b)
White solid (1c)
White solid (2c)
White solid (3c)
White solid (4c)
White solid (5c)
White solid (6c)
White solid (7c)
White solid (8c)
White solid (9c)
White solid (10c)
White solid (11c)
115e116
84e86
C
21H16Cl2OS
387
353
398
397
457
487
318
483
523
455
515
418
384
429
428
488
518
350
546
586
518
578
Table 5
C21H17ClOS
C21H16ClNO3S
C21H17BrOS
Minimum inhibitory concentration (MIC) in
bacterial strains evaluated by microdilution method.
mg/ml of chalcone derivatives against
124e126
114e116
131e133
140e142
117e119
125e126
143e145
100e102
135e137
175e177
140e141
168e170
173e174
160e161
200e201
138e140
158e160
184e185
161e162
188e190
S No. Drug Gram positive
Gram negative
C
23H21BrO3S
C24H23BrO4S
C21H18OS
C31H30OS2
C29H24Cl2OS2
C29H26OS2
C31H30O3S2
Bacillus subtilis Staphylococcus Salmonella
Pseudomonas
(
m
g/ml)
aureus (
m
g/ml) typhimurium aeruginosa
g/ml) g/ml)
(m
(m
1
2
3
4
5
6
7
8
Ampicillin 250
500
500
250
125
125
125
62.50
125
62.50
62.50
250
125
125
Kanamycin
7.81
15.62
125
250
125
1c
2c
3c
4c
5c
6c
7c
8c
9c
10c
11c
15.62
62.50
62.50
62.50
62.50
31.25
31.25
62.50
31.25
C
21H16Cl2O3S
125
62.50
250
1.95
1.95
1.95
31.25
15.62
250
62.50
62.50
62.50
62.50
125
125
62.50
250
C21H17ClO3S
C21H16ClNO5S
C21H17BrO3S
C23H21BrO5S
C24H23BrO6S
C21H18O3S
C31H30O5S2
C
C29H26O5S2
C31H30O7S2
9
10
11
12
13
29H24Cl2O5S2
125
31.25
62.50
250
62.50
125
62.50

N.K. Konduru et al. / European Journal of Medicinal Chemistry 59 (2013) 23e30
27
Table 6
3.1.1.1. 1-(4-Chlorophenyl)-3-(4-chlorophenyl)-3-phenylsulfenylprop-
ane-1-one (1b) [32]. Yield 90%; White solid; mp: 115e116 ꢀC; 1H
Minimum inhibitory concentration (MIC) in
fungus evaluated by microdilution method.
mg/ml of chalcone derivatives against
NMR (CDCl3, 500 MHz):
2H), 7.31e7.29 (m, 2H), 7.26e7.18 (m, 7H), 4.57 (t, J ¼ 7.5 Hz, 1H),
3.59e3.49 (m, 2H). 13C NMR (CDCl3, 125 MHz):
195.5, 139.95,
d
7.81 (d, J ¼ 8.5 Hz, 2H), 7.41 (d, J ¼ 8.5 Hz,
S No.
Drug
Aspergillus niger
g/ml)
Candida albicans
(mg/ml)
(
m
d
1
2
3
4
5
6
7
8
Amphotericin-B
Nystatin
1c
2c
3c
4c
5c
6c
7c
8c
9c
10c
11c
500
15.62
7.81
31.25
1.95
1.95
125
15.62
3.90
3.90
1.95
1.95
250
139.69, 134.86, 137.57, 133.57, 133.06, 130.73, 129.48, 129.16, 129.03,
128.65, 127.94, 47.6, 44.5. IR (KBr, cmꢁ1) v: 3070, 2913, 1679, 1588,
1217. ESI-MS m/z: 387 [M þ H]þ. Anal. Calc. for C21H16Cl2OS: C,
65.12; H, 4.16; S, 8.28. Found: C, 64.01; H, 4.13; S, 8.52.
7.81
15.62
125
62.50
62.50
15.62
7.81
7.81
31.25
125
3.1.1.2. 1-Phenyl-3-(4-chlorophenyl)-3-phenylsulfenylpropane-1-one
(2b) [28]. Yield 90%; White solid; mp: 84e86 ꢀC; 1H NMR (CDCl3,
9
500 MHz):
(m, 11H), 4.51 (m, 1H), 3.59e3.51 (m, 2H). 13C NMR (CDCl3,
125 MHz): 194.6, 141.04, 139.96, 134.68, 137.75, 134.57, 133.60,
d
7.83 (d, J ¼ 16 Hz, 2H), 7.46 (d, J ¼ 6.5 Hz,1H), 7.39e7.15
10
11
12
13
125
125
d
125
130.37, 129.48, 129.26, 129.03, 128.76, 127.94, 47.6, 44.6. IR (KBr,
cmꢁ1) v: 3057, 2926, 2890, 1679, 1489, 1325. ESI-MS m/z: 353
[M þ H]þ. Anal. Calc. for C21H17ClOS: C, 71.48; H, 4.86; S, 9.09.
Found: C, 71.41; H, 4.85; S, 8.89.
Compounds 2c, 3c, 8c and 9c have shown excellent antifungal
activity (MIC: 1.95 g/ml) against C. albicans. Compounds 6c, 7c
have shown better antifungal activity (MIC: 3.90 g/ml), 5c has
shown the same activity (MIC: 15.62 g/ml) as Amphotericin-B
against C. albicans while others have lower activity (MIC ꢂ 125e
62.50 g/ml). Compounds 6c, 7c have shown better antifungal
activity (MIC: 7.81 g/ml) against A. niger. Compounds 1c, 5c have
shown sensible antifungal activity (MIC: 15.62 g/ml) and 8c (MIC:
31.25 g/ml), 3c, 4c (MIC: 62.50 g/ml) have shown good antifungal
activity against A. niger as compare to Amphotericin-B. Highly
electron releasing group (Tri-OMe) or without substitutions on
aromatic ring containing compounds 6c, 7c have shown equal
activity compare to standard drug Nystatin against A. niger. Against
C. albicans electron withdrawing group compounds 2c, 3c, 9c have
m
m
3.1.1.3. 1-(4-Chlorophenyl)-3-(3-nitrophenyl)-3-phenylsulfenylprop-
ane-1-one (3b). Yield 92%; White solid; mp: 124e126 ꢀC; 1H NMR
m
(CDCl3, 500 MHz):
d
8.16 (s, 1H), 8.0 (dd, J ¼ 8 Hz, 1.5 Hz, 1H), 7.82
m
(d, J ¼ 7.5 Hz, 2H), 7.6 (d, J ¼ 7.5 Hz, 1H), 7.47e7.29 (m, 3H), 7.28e7.2
(m, 5H), 4.67 (t, J ¼ 7 Hz, 1H), 3.65e3.59 (m, 2H). 13C NMR (CDCl3,
m
m
125 MHz):
d 194.97, 148.22, 143.56, 140.17, 134.55, 134.20, 133.48,
m
132.67, 129.44, 129.04, 128.37, 127.48, 127.13, 122.58, 122.39, 47.69,
44.07. IR (KBr): 3078, 3056, 2917, 1683, 1535, 1223 cmꢁ1. ESI-MS
m/z: 398 [M þ H]þ. Anal. Calc. for C21H16ClNO3S: C, 63.39; H,
4.05; N, 3.52; S, 8.06. Found: C, 63.51; H, 4.09; N, 3.70; S, 8.21.
3.1.1.4. 1-(4-Bromophenyl)-3-phenyl-3-phenylsulfenylpropane-1-one
(4b) [28]. Yield 95%; White solid; mp: 114e116 ꢀC; 1H NMR (CDCl3,
shown excellent antifungal activity (MIC: 1.95
standards drugs Amphotericin-B and Nystatin.
mg/ml) compare to
500 MHz):
7.22 (m, 10H), 4.45e4.52 (m, 1H), 3.62e3.50 (m, 2H). 13C NMR
(CDCl3, 125 MHz): 196.1, 141.0, 135.4, 134.59, 133.65, 132.8, 131.96,
d
7.72 (dd, J ¼ 5 Hz, 1.5 Hz, 2H), 7.58e7.54 (m, 2H), 7.32e
d
3. Experimental section
129.62, 128.93, 128.54, 127.79, 127.67, 127.57, 48.27, 44.67. IR (KBr,
cmꢁ1) v: 3067, 3023, 2019, 1684, 1577, 1222. ESI-MS m/z: 397
[M þ H]þ. Anal. Calc. for C21H17BrOS: C, 63.48; H, 4.31; S, 8.07.
Found: C, 63.49; H, 4.28; S, 8.11.
3.1. Chemistry
All the required chemicals were purchased from Merck and
Aldrich Chemical Company. Pre-coated aluminum sheets (silica gel
60 F254, Merck) were used for thin-layer chromatography (TLC) and
spots were visualized under UV light. Elemental analysis was
carried out on C, H, N, S Elementar (Vario EL-III) and the results
were within ꢃ0.3% of the theoretical values. IR spectra were
recorded with KBr on Thermo Nicolet FT-IR spectrophotometer. 1H
NMR and 13C NMR spectra were recorded respectively on Bruker
Spectrospin DPX 500 MHz and Bruker Spectrospin DPX 125 MHz
spectrometer using CDCl3 as a solvent and trimethylsilane (TMS) as
an internal standard. Splitting patterns are designated as follows; s,
3.1.1.5. 1-(4-Bromophenyl)-3-(3,4-dimethoxyphenyl)-3-phenylsulfeny-
lpropane-1-one (5b). Yield 95%; White solid; mp: 131e133 ꢀC; 1H
NMR(CDCl3, 500 MHz):
d
7.61 (d, J¼ 8.5Hz, 2H),7.43(d,J¼ 8.5Hz, 2H),
7.38 (d, J ¼ 8 Hz,1H), 7.2e7.25 (m, 2H), 7.2 (t, J ¼ 7Hz,1H)7.16e7.08(m,
2H), 6.73 (t, J ¼ 6.5 Hz, 2H), 4.40e4.38 (m,1H), 3.70 (s, 6H), 3.51e3.33
(m, 2H). 13C NMR (CDCl3, 125 MHz):
d 189.44, 151.62, 149.27, 147.83,
145.60, 137.18, 134.56, 131.85, 129.96, 127.64, 127.60, 123.33, 119.41,
111.12, 110.10, 56.0, 55.97, 47.61, 43.97. IR (KBrcmꢁ1) v: 3073, 3009,
2925, 1681, 1581, 1253. ESI-MS m/z: 457 [M þ H]þ. Anal. Calc. For
C23H21BrO3S: C, 60.40; H, 4.63; S, 7.01. Found: C, 60.32; H, 4.71; S, 7.06.
singlet; d, doublet; m, multiplet. Chemical shift (d) values are given
in ppm.
3.1.1.6. 1-(4-Bromophenyl)-3-(3,4,5-trimethoxyphenyl)-3-phenylsul-
fenylpropane-1-one (6b). Yield 89%; White solid; mp: 140e142 ꢀC;
3.1.1. General procedure for synthesis of compounds (1be7b)
To a stirred solution of -unsaturated carbonyl compound
1H NMR (CDCl3, 500 MHz):
d
7.88 (d, J ¼ 8.5 Hz, 2H), 7.74 (m, 3H),
a
,b
7.58 (d, J ¼ 7.5 Hz, 2H), 7.27e7.24 (m, 2H), 6.50 (s, 2H), 4.45 (t,
(1 mmol) in DCM was added thiophenol (1.2 mmol, 132 mg), fol-
lowed by sodium metal (1.2 mmol, 27.6 mg) at room temperature.
The reaction mixture was stirred for appropriate time given in
Table 2. TLC monitoring, after completion of reaction filtered excess
amount of sodium then the reaction mixture was quenched with
water and extracted with DCM (3 ꢄ 8 ml), washed with brine
solutions (10 ml). The combined organic layers dried over anhy-
drous Na2SO4 and the solvent evaporated in vacuo. Pure sulfide was
obtained by recrystallization from methanol.
J ¼ 8.5 Hz, 1H), 3.78 (s, 6H), 3.75 (s, 3H), 3.6e3.48 (m, 2H). 13C NMR
(CDCl3, 125 MHz):
d 196.12, 153.09, 137.22, 136.54, 135.46, 134.01,
133.06, 131.99, 129.60, 128.96, 128.59, 127.81, 104.77, 56.11, 55.21,
48.77, 44.71. IR (KBr, cmꢁ1) v: 3065, 2939, 2830, 1683, 1586, 1131.
ESI-MS m/z: 487 [M þ H]þ. Anal. Calc. For C24H23BrO4S: C, 59.14; H,
4.76; S, 6.58. Found: C, 59.24; H, 4.76; S, 6.66.
3.1.1.7. 1-Phenyl-3-phenyl- 3-phenylsulfenylpropane-1-one (7b) [28].
Yield 95%; White solid; mp: 117e119 ꢀC; 1H NMR (CDCl3, 500 MHz):

28
N.K. Konduru et al. / European Journal of Medicinal Chemistry 59 (2013) 23e30
d
7.87 (d, J ¼ 7.5 Hz, 2H), 7.54 (t, J ¼ 8 Hz, 1H), 7.43 (t, J ¼ 7.5 Hz, 2H),
7.34e7.32 (m, 4H), 7.27e7.17 (m, 6H), 4.57e4.54 (m, 1H), 3.7e3.5
(m, 2H). 13C NMR (CDCl3, 125 MHz):
197.04, 141.21, 136.72,
3.1.2.5. 1-(4-Bromophenyl)-3-(3,4-dimethoxyphenyl)-3-(phenyl-
sulfonyl)propane-1-one (5c). Yield 86%; white solid; mp: 160e
d
161 ꢀC; 1H NMR (CDCl3, 500 MHz):
d
7.82 (d, J ¼ 8.5 Hz, 2H), 7.62
134.33, 133.29, 132.8, 128.9, 128.62, 128.51, 128.13, 127.84, 127.62,
127.47, 48.23, 44.72. IR (KBr, cmꢁ1) v: 3057, 2900, 1673, 1446, 1331,
1584. ESI-MS m/z: 319 [M þ H]þ. Anal. Calc. For C21H18OS: C, 79.21;
H, 5.70; S, 10.07. Found: C, 79.11; H, 5.73; S, 10.18.
(d, J ¼ 8 Hz, 2H), 7.57e7.55 (m, 2H), 7.41 (t, J ¼ 7.5 Hz, 2H), 6.75 (dd,
J ¼ 8.5 Hz, 2 Hz, 1H), 6.69 (d, J ¼ 13.5 Hz, 1H), 6.58 (s, 2H), 4.84 (dd,
J ¼ 9.5 Hz, 3 Hz, 1H), 4.08 (dd, J ¼ 18 Hz, 3.5 Hz, 1H), 3.87e3.83 (m,
1H), 3.81 (s, 3H), 3.69 (s, 3H). 13C NMR (CDCl3, 125 MHz):
d 194.13,
149.44, 148.69, 136.92, 134.89, 133.73, 132.13,129.66, 129.08, 128.81,
126.55, 124.48, 122.08, 112.69, 110.87, 66.18, 55.82, 53.35, 36.73. IR
(KBr, cmꢁ1) v: 3090, 2933, 1690, 1517. Anal. Calc. for C23H21BrO5S
(488.03): C, 56.45; H, 4.33; S, 6.55. Found: C, 56.55; H, 4.30; S, 6.25.
3.1.2. General procedure for synthesis of compounds (1ce7c)
To a stirred solution of chalcone sulfide (1 mmol) in DCM was
added m-CPBA (2.2 mmol, 379.5 mg) at 0 ꢀC portion wise for
15 min, reaction mixture stirred at this temperature for 30 min then
warmed to room temperature and stirred for appropriate time in
Table 2. TLC monitoring, After completion of reaction, the reaction
was diluted with DCM (8 ml) and washed with 5% aqueous K2CO3
(3 ꢄ 8 ml) and 5% NaHCO3 (10 ml) solution for removing excess m-
CPBA, then aqueous layer extracted with DCM (3 ꢄ 10 ml), the
combined organic layers dried over anhydrous Na2SO4, and solvent
evaporated in vacuo. Pure sulfone was obtained by recrystallization
from methanol.
3.1.2.6. 1-(4-Bromophenyl)-3-(3,4,5-trimethoxyphenyl)-3-(phenyl-
sulfonyl) propane-1-one (6c). Yield 80%; white solid; mp: 200e
201 ꢀC; 1H NMR (CDCl3, 500 MHz):
d
7.84 (d, J ¼ 8 Hz, 2H), 7.63
(d, J ¼ 17 Hz, 2H), 7.60 (d, J ¼ 6 Hz, 3H), 7.43e7.37 (m, 2H), 6.33 (s,
2H), 4.83 (d, J ¼ 9.5 Hz, 1H), 4.08 (d, J ¼ 18 Hz, 1H), 3.93e3.71 (m,
1H), 3.78 (s, 3H), 3.65 (s, 6H). 13C NMR (CDCl3, 125 MHz):
d 194.5,
153.06, 136.82, 133.77, 132.18, 131.58, 129.67, 129.14, 128.80, 127.68,
106.85, 100.00, 66.66, 56.12, 53.45, 36.64. IR (KBr, cmꢁ1) v: 3065,
2921, 2847, 1693, 1587, 1134. Anal. Calc. for C24H23BrO6S (518.04): C,
55.50; H, 4.46; S, 6.17. Found: C, 55.60; H, 4.50; S, 6.30.
3.1.2.1. 1,3-Bis(4-chlorophenyl)-3-(phenylsulfonyl)propan-1-one
(1c). Yield 89%; white solid; mp: 175e177 ꢀC; 1H NMR (CDCl3,
500 MHz):
d
7.86 (dd, J ¼ 8.5 Hz, 1.5 Hz, 2H), 7.62e7.56 (m, 3H),
3.1.2.7. 1-Phenyl-3-phenyl- 3-phenylsulfonylpropane-1-one (7c) [28].
Yield 93%; white solid; mp: 138e140 ꢀC; 1H NMR (CDCl3, 500 MHz):
7.46e7.42 (m, 4H), 7.18 (d, J ¼ 8.5 Hz, 2H), 7.12 (d, J ¼ 8.5 Hz, 2H),
4.96 (dd, J ¼ 9.5 Hz, 3 Hz, 1H), 4.12 (dd, J ¼ 18 Hz, 3.5 Hz, 1H), 3.86e
d
7.94 (dd, J ¼ 5 Hz, 1 Hz, 2H), 7.57e7.37 (m, 8H), 7.26e7.19 (m, 5H),
4.95e4.93 (m,1H), 4.13 (dd, J ¼ 18 Hz, 3.5 Hz,1H), 3.98e3.91 (m,1H).
13CNMR (CDCl3,125MHz):
194.88,136.93,136.1,133.74,133.7,132.5,
3.80 (m, 1H). 13C NMR (CDCl3, 125 MHz):
d 193.59, 140.40, 136.60,
135.01, 134.25, 134.00, 133.25, 131.02, 130.93, 129.51, 129.37, 129.15,
128.77, 65.74, 36.85. IR (KBr, cmꢁ1) v: 3060, 2919, 2843, 1687, 1304,
1142. Anal. Calc. for C21H16Cl2O3S (418.02): C, 60.15; H, 3.85; S, 7.65.
Found: C, 60.26; H, 3.87; S, 7.25.
d
129.8,129.03,128.83,128.78,128.76,128.5,128.15, 66.51, 36.9. IR (KBr,
cmꢁ1) v: 3065, 2926, 1687, 1306, 1142. Anal. Calc. for C21H18O3S
(350.09): C, 71.98; H, 5.18; S, 9.15. Found: C, 72.06; H, 5.20; S, 9.31.
3.1.2.2. 1-Phenyl-3-(4-chlorophenyl)-3-(phenylsulfonyl)propane-1-
3.1.3. General procedure for synthesis of compounds (8be11b)
one (2c) [28]. Yield 90%; white solid; mp: 140e141 ꢀC; 1H NMR
To a stirred solution of a,b-unsaturated carbonyl compound
(CDCl3, 500 MHz):
d
7.93 (d, J ¼ 7.5 Hz, 2H), 7.62e7.57 (m, 4H), 7.5e
(1 mmol) in DCM was added thiophenol (2.5 mmol, 275 mg) fol-
lowed by sodium metal (2.5 mmol, 57.5 mg) at room temperature.
The reaction mixture was stirred appropriate time given in Table 3.
TLC monitoring, after completion of reaction filtered excess amount
of sodium then the reaction mixture was quenched with water and
extracted with DCM (3 ꢄ 8 ml), washed with brine solutions
(10 ml). The combined organic layers dried over anhydrous Na2SO4
and the solvent evaporated in vacuo. Pure sulfide was obtained by
recrystallization from methanol.
7.42 (m, 4H), 7.18 (d, J ¼ 8.5 Hz, 2H), 7.13 (d, J ¼ 8.5 Hz, 2H), 4.9 (dd,
J ¼ 5 Hz, 3.5 Hz, 1H), 4.12 (dd, J ¼ 17.5 Hz, 3 Hz, 1H), 3.89 (m, 1H). 13C
NMR (CDCl3, 125 MHz):
d 194.69, 136.74, 135.97, 134.96, 133.98,
133.87, 131.15, 131.02, 128.99, 128.95, 128.83, 128.76, 128.13, 65.85,
36.92. IR (KBr, cmꢁ1) v: 3104, 2940, 1687, 1302, 1147. Anal. Calc. for
C21H17ClO3S (384.06): C, 65.53; H, 4.45; S, 8.33. Found: C, 65.43; H,
4.49; S, 8.13.
3.1.2.3. 1-(4-Chlorophenyl)-3-(3-nitrophenyl)-3-phenylsulfonylprop-
ane-1-one (3c). Yield 88%; white solid; mp: 168e170 ꢀC; 1H NMR
3.1.3.1. 1,5-Di(4-methylphenyl)-1,5-bis(phenylsulfenyl)pentan-3-one
(CDCl3, 500 MHz):
d
8.13 (dd, J ¼ 7 Hz, 1.5 Hz, 1H), 8.022 (m, 1H),
(8b). Yield 92%; White solid; mp: 125e126 ꢀC; 1H NMR (CDCl3,
7.88 (dd, J ¼ 7 Hz, 2 Hz, 2H), 7.64e7.58 (m, 4H), 7.47e7.43 (m, 5H),
500 MHz):
d
7.36 (d, J ¼ 7.5 Hz, 2H), 7.23e7.04 (m, 16H), 4.32e4.28
5.0 (dd, J ¼ 10 Hz, 3.5 Hz, 1H), 4.16 (dd, J ¼ 18 Hz, 3.5 Hz, 1H), 3.93e
(m, 2H), 2.95e2.77 (m, 4H), 2.35 (s, 6H). 13C NMR (CDCl3, 125 MHz):
3.88 (m, 1H). 13C NMR (CDCl3, 125 MHz):
d
201.13, 138.79, 136.71,
d 204.9, 137.6, 137.0, 134.2, 132.6, 128.85, 126.91, 125.15, 127.42,
135.17, 134.53, 133.77, 130.29, 129.81, 129.36, 129.17, 129.05, 128.69,
128.60, 127.93, 127.08, 65.65, 41.53. IR (KBr, cmꢁ1) v: 3075, 2962,
1684, 1533. Anal. Calc. for C21H16ClNO5S (429.04): C, 58.67; H, 3.75;
N, 3.26; S, 7.46. Found: C, 59.00; H, 3.81; N, 3.16; S, 7.34.
49.51, 47.42, 21.12. IR (KBr, cmꢁ1) v: 3030, 2921, 2878, 1715, 1375.
ESI-MS m/z: 483 [M þ H]þ. Anal. Calc. for C31H30OS2: C, 77.14; H,
6.26; S, 13.29. Found: C, 77.21; H, 6.28; S, 13.38.
3.1.3.2. 1,5-Di(4-chlorophenyl)-1,5-bis(phenylsulfenyl)pentan-3-one
3.1.2.4. 1-(4-Bromophenyl)-3-phenyl-3-(phenylsulfonyl) propane-1-
(9b). Yield 90%; White solid; mp: 143e145 ꢀC; 1H NMR (CDCl3,
one (4c) [28]. Yield 92%; white solid; mp: 173e174 ꢀC; 1H NMR
500 MHz):
J ¼ 7 Hz, 2H), 7.07 (d, J ¼ 7 Hz, 2H), 6.99 (d, J ¼ 7 Hz, 2H), 4.56e4.52
(m, 2H), 3.0e2.79 (m, 4H). 13C NMR (CDCl3, 125 MHz):
204.5,
d
7.48 (d, J ¼ 1.5 Hz, 1H), 7.28e7.25 (m, 11H), 7.14 (d,
(CDCl3, 500 MHz):
d
7.94 (dd, J ¼ 7 Hz, 1.5 Hz, 1H), 7.81 (d,
J ¼ 8.5 Hz, 2H), 7.62 (d, J ¼ 8.5 Hz, 2H), 7.56e7.52 (m, 3H), 7.38 (t,
J ¼ 8.5 Hz, 2H), 7.2e7.16 (m, 4H), 4.9 (dd, J ¼ 9.5 Hz, 3.5 Hz, 1H), 4.1
(dd, J ¼ 16 Hz, 3.5 Hz, 1H), 3.91e3.87 (m, 1H). 13C NMR (CDCl3,
d
140.5, 133.88, 132.91, 128.6, 128.5, 127.68, 127.40, 126.84, 49.2, 47.6.
IR (KBr, cmꢁ1) v: 3056, 2917, 1709, 1483, 1090. ESI-MS m/z: 523
[M þ H]þ. Anal. Calc. For C29H24Cl2OS2: C, 66.53; H, 4.62; S, 12.25.
Found: C, 66.63; H, 4.61; S, 12.42.
125 MHz):
d 193.98, 145.45, 136.94, 134.86, 133.79, 132.42, 131.96,
130.79, 130.05, 129.71, 129.03, 128.77, 128.54, 66.44, 36.85. IR (KBr,
cmꢁ1) v: 3070, 2917, 2847, 1684, 1585, 1299. Anal. Calc. for
C21H17BrO3S (428.01): C, 58.75; H, 3.99; S, 7.47. Found: C, 58.66; H,
3.96; S, 7.27.
3.1.3.3. 1,5-Diphenyl-1,5-bis(phenylsulfenyl)pentan-3-one (10b) [33].
Yield 90%; White solid; mp: 100e102 ꢀC; 1H NMR (CDCl3,

N.K. Konduru et al. / European Journal of Medicinal Chemistry 59 (2013) 23e30
29
500 MHz):
d
7.25e7.10 (m, 20H), 4.45e4.4.50 (m, 2H), 3.08e2.78
3.1.4.4. 1,5-Di(4-methoxyphenyl)-1,5-bis(phenylsulfonyl)pentan-3-
(m, 4H). 13C NMR (CDCl3, 125 MHz):
d
204.6, 140.68, 133.9, 132.86,
one (11c). Yield 80%; white solid; mp: 188e190 ꢀC; 1H NMR (CDCl3,
128.87, 128.49, 127.66, 127.47, 126.84, 49.39, 47.76. IR (KBr, cmꢁ1) v:
3056, 3021, 2886, 1716, 1321. ESI-MS m/z: 455 [M þ H]þ. Anal. Calc.
For C29H26OS2: C, 76.61; H, 5.76; S, 14.11. Found: C, 76.70; H, 5.81; S,
14.25.
500 MHz):
d
7.49 (d, J ¼ 6.5 Hz, 2H), 7.43 (d, J ¼ 6.5 Hz, 4H), 7.37 (dd,
J ¼ 8 Hz, 7.5 Hz, 4H), 6.92 (d, J ¼ 8.5 Hz, 2H), 6.84 (d, J ¼ 8.5 Hz, 2H),
6.71 (d, J ¼ 8.5 Hz, 2H), 6.62 (d, J ¼ 8.5 Hz, 2H), 4.95 (m, 2H), 3.75 (s,
6H), 3.50 (dddd, J ¼ 50.5, 28 Hz,18 Hz, 9.5 Hz, 2H), 3.36e3.31 (m,1H),
3.18e3.12(m,1H).13CNMR(CDCl3,125MHz):
d200.10,137.56,135.12,
3.1.3.4. 1,5-Di(4-methoxyphenyl)-1,5-bis(phenylsulfenyl)pentan-3-
132.86, 130.64, 129.10, 128.91, 128.70, 124.97, 65.01, 58.06, 42.45. IR
(KBr, cmꢁ1) v: 3019, 2995,1707,1356,1155. Anal. Calc. for C31H30O7S2
(578.14): C, 64.34; H, 5.23; S, 11.08. Found: C, 64.55; H, 5.19; S, 11.21.
one (11b). Yield 89%; White solid; mp: 135e137 ꢀC; 1H NMR (CDCl3,
500 MHz):
d
7.36 (d, J ¼ 6.5 Hz, 2H), 7.30 (d, J ¼ 6.5 Hz, 2H), 7. 28 (dd,
J ¼ 8 Hz, 7.5 Hz, 4H), 6.91 (d, J ¼ 8.5 Hz, 2H), 6.81 (d, J ¼ 8.5 Hz, 2H),
6.66 (d, J ¼ 8.5 Hz, 2H), 6.62 (d, J ¼ 8.5 Hz, 2H), 4.55 (m, 2H), 3.71 (s,
6H), 3.44 (m, 2H), 3.36e3.31 (m, 2H). 13C NMR (CDCl3, 125 MHz):
3.2. Antimicrobial activity
d
199.10, 135.56, 134.02, 131.83, 129.64, 129.01, 128.81, 128.64,
3.2.1. Test strain
126.65, 55.06, 49.01, 42.45. IR (KBr, cmꢁ1) v: 3062, 2954, 2842, 1713,
1509, 1248, 741. ESI-MS m/z: 515 [M þ H]þ. Anal. Calc. For
C31H30O3S2: C, 72.34; H, 5.87; S, 12.46. Found: C, 72.36; H, 5.91; S,
12.14.
The clinical isolates of A. niger and C. albicans were obtained
from the Department of Microbiology, J. N. Medical College, A.M.U.
Aligarh, India, as described earlier (Nasti et al., 2006). The isolate
was sub-cultured on Sabouraud Dextrose Agar at 37 ꢀC for 48e72 h.
Both Gram (þ) bacteria (B. subtilis and S. aureus) and Gram (ꢁ)
bacteria (P. aeruginosa and S. typhimurium) were also obtained from
the Department of Microbiology, J. N. Medical College, A.M.U. Ali-
garh, India, and used to evaluate the antibacterial effectiveness of
the test compounds.
3.1.4. General procedure for synthesis of compounds (8ce11c)
To a stirred solution of chalcone sulfide (1 mmol) in DCM was
added m-CPBA (4.5 mmol, 776.5 mg) at 0 ꢀC portion wise for
25 min, reaction mixture stirred at this temperature for 30 min
then warmed to room temperature and stirred appropriate time in
Table 3. TLC monitoring, after completion of reaction, the reaction
was diluted with DCM (8 ml) and washed with 5% aqueous K2CO3
(3 ꢄ 8 ml) and NaHCO3 (10 ml) solution for removing excess m-
CPBA, then aqueous layer extracted with DCM (3 ꢄ 10 ml), the
combined organic layers dried over anhydrous Na2SO4, and solvent
evaporated in vacuo. Pure sulfone was obtained by recrystallization
from methanol.
3.2.2. Antifungal susceptibility testing
Minimum inhibitory concentration (MIC) is the lowest concen-
tration of an antimicrobial compound that inhibits the visible
growth of a microorganism. The minimum inhibitory concentration
(MIC) of standard antifungal drugs viz. Nystatin and Amphotericin-
B was determined by the broth microdilution method as described
by the National Committee for Clinical Laboratory Standards
recommendations (NCCLS, 1997). MIC values of the synthesized
compounds against fungal isolates were determined on the basis of
micro-well dilution method following NCCLS recommendations
[30]. A stock of chemically synthesized compounds was made at
a concentration of 10 mg/ml in DMSO, which was further converted
to working solution of concentration 1 mg/ml solution in methanol.
3.1.4.1. 1,5-Di(4-methylphenyl)-1,5-bis(phenylsulfonyl)pentan-3-one
(8c). Yield 90%; white solid; mp: 158e160 ꢀC; 1H NMR (CDCl3,
500 MHz):
d
8.05 (d, J ¼ 2 Hz, 1H), 7.57e7.49 (m, 6H), 7.40e7.37 (m,
4H), 6.92 (d, J ¼ 16 Hz, 4H), 6.81 (d, J ¼ 8 Hz, 3H), 4.95 (dd, J ¼ 9 Hz,
4.5 Hz, 2H), 3.64 (dd, J ¼ 17.5 Hz, 4.5 Hz, 2H), 3.17e3.12 (m, 2H), 2.14
(s, 6H). 13C NMR (CDCl3, 125 MHz):
d
193.51, 140.71, 136.20, 135.65,
Using a micropipette, 100 ml of media was dispensed into wells of
134.81, 134.35, 129.53, 128.90, 124.55, 60.55, 39.66, 20.92. IR (KBr,
cmꢁ1) v: 3065, 2923, 1769, 1302, 1145 cmꢁ1. Anal. Calc. for
C31H30O5S2 (546.15): C, 68.11; H, 5.53; S, 11.73. Found: C, 68.23; H,
5.57; S, 11.90.
pre-sterilized microtitre plate (experiment was done in triplicate).
Two fold serial dilutions were carried out from the well # 1 to the
well # 10 and excess media (100
ml) was discarded from the last
well (# 10). Liquid broth culture of test organism was grown to
a suitable phase in Yeast, Peptone, and D-Glucose (YPD) media for
3.1.4.2. 1,5-Di(4-chlorophenyl)-1,5-bis(phenylsulfonyl)pentan-3-one
12e18 h at 37 ꢀC. The optical density of liquid culture was deter-
(9c). Yield 88%; white solid; mp: 184e185 ꢀC; 1H NMR (CDCl3,
mined at 600 nm and diluted in such a way that each well received
500 MHz):
d
8.07 (d, J ¼ 3 Hz, 1H), 7.96 (d, J ¼ 3 Hz, 1H), 7.56 (q, 3H),
104 cfu/100
ml of fungal suspension.
7.51e7.37 (m, 8H), 7.19 (d, J ¼ 8.5 Hz, 1H), 7.09 (d, J ¼ 8.5 Hz, 1H),
6.96 (d, J ¼ 8.5 Hz, 1H), 6.85 (d, J ¼ 8.5 Hz, 2H), 4.98e4.93 (dd,
J ¼ 9 Hz, 4.5 Hz, 2H), 3.56 (dddd, J ¼ 35 Hz, 17.5 Hz, 4.5 Hz, 2H), 3.33
3.2.3. Antibacterial activity
MIC values of the compounds against bacterial isolates were
determined on the basis of micro-well dilution method following
NCCLS recommendations [30]. In this method we made stock of
chemically synthesized compounds at a concentration of 10 mg/ml
in DMSO, which was further converted to working solution of
concentration 1 mg/ml solution in methanol. Using a micropipette,
(m, 1H), 3.15 (m, 1H). 13C NMR (CDCl3, 125 MHz):
d 196.12, 136.35,
135.23, 134.09, 130.79, 130.61, 130.33, 128.99, 128.74, 65.31, 41.51. IR
(KBr, cmꢁ1) v: 3065, 2920, 2847, 1724, 1301. Anal. Calc. for
C29H24Cl2O5S2 (586.04): C, 59.28; H, 4.12; S, 10.92. Found: C, 59.37;
H, 4.09; S, 10.68.
100 ml of media into all wells of pre-sterilized microtitre plate was
3.1.4.3. 1,5-Di(phenyl)-1,5-bis(phenylsulfonyl)pentan-3-one
(10c).
dispensed (experiment was done in triplicate). Two fold serial
dilutions were carried out from the well # 1 to the well # 10 and
Yield 89%; white solid; mp: 161e162 ꢀC; 1H NMR (CDCl3, 500 MHz):
d
7.54e7.46 (m, 5H), 7.41 (d, J ¼ 8 Hz, 1H), 7.36e7.29 (m, 5H), 7.18 (t,
excess media (100 ml) was discarded from the last well (# 10).
J ¼ 6.5 Hz, 3H), 7.09 (t, J ¼ 7 Hz, 3H), 7.02 (d, J ¼ 7.5 Hz, 1H), 6.92 (d,
J ¼ 7.5 Hz, 2H), 4.92 (m, 2H), 3.62 (dd, J ¼ 17.5 Hz, 4.5 Hz, 1H), 3.53
(dd, J ¼ 18 Hz, 4.5 Hz, 1H), 3.41 (m, 1H), 3.21 (m, 1H). 13C NMR
Liquid broth culture of test organism was grown to log phase in
Luria Bertani Broth (Nutrient Broth) for 12e18 h at 37 ꢀC. The
optical density of liquid culture was determined at 600 nm and
(CDCl3, 125 MHz):
d
201.1, 136.53, 133.92, 131.83, 129.54, 129.01,
diluted in such a way that each well received 107 cfu/100
ml of
128.81, 128.54, 126.55, 66.01, 41.42. IR (KBr, cmꢁ1) v: 3066, 2924,
1723,1304,1143, 691. Anal. Calc. for C29H26O5S2 (518.12): C, 67.16; H,
5.05; S, 12.36. Found: C, 67.06; H, 5.10; S, 12.56.
bacterial culture. Appropriate positive and negative control was
also included in the study. Positive control contained only microbial
cells where as negative control contained only standard drug

30
N.K. Konduru et al. / European Journal of Medicinal Chemistry 59 (2013) 23e30
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solution (Ampicillin, Kanamycin). All experimental procedures
were performed under sterile condition using bio-safety hood and
microtitre plates were incubated at 37 ꢀC for 12e18 h.
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4. Conclusion
We have developed an efficient route for the synthesis of chal-
cone based sulfones and bisulfones using m-CPBA as an oxidizing
agent. They were evaluated for their antibacterial and antifungal
activities. Compounds 2c, 3c, 6c, 7c, 8c and 9c were demonstrated
high antifungal activity against C. albicans. Compound 1c have
shown better antibacterial activity against B. subtilis. Compounds
5c, 6c, 7c have shown admirable antibacterial activity against S.
typhimurium. Other sulfone derivatives have shown fair to medium
antibacterial and antifungal activities.
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8315e8327.
Acknowledgments
[22] K. Bahrami, Tetrahedron Lett. 47 (2006) 2009e2012.
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Authors are grateful to reviewers valuable comments & sugges-
tions and Council of Scientific and Industrial Research (CSIR) for NKK
fellowship and DST New Delhi, India for financial assistance.
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