The synthesis and screening of the antimicrobial activity of some novel 3-(furan-2-yl)-1-(aryl)-3-(phenylthio) propan-1-one derivatives

Article abstract of DOI:10.1007/s00044-009-9279-4

A series of thiophenol adducts (3a-m) were prepared by addition of thiophenol to chalcones (1a-m) in the presence of a catalytic amount of KOt-Bu in solvent free conditions. In addition, the antibacterial and antifungal in vitro properties were tested aga

Full text of DOI:10.1007/s00044-009-9279-4

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2011) 20:109–115
DOI 10.1007/s00044-009-9279-4
ORIGINAL RESEARCH
The synthesis and screening of the antimicrobial activity
of some novel 3-(furan-2-yl)-1-(aryl)-3-(phenylthio)
propan-1-one derivatives
•
•
Mustafa Ceylan Meliha Burcu Gu¨rdere
˙
Isa Karaman Hayreddin Gezegen
•
Received: 2 April 2009 / Accepted: 3 December 2009 / Published online: 5 January 2010
Ó Springer Science+Business Media, LLC 2010
Abstract A series of thiophenol adducts (3a–m) were
prepared by addition of thiophenol to chalcones (1a–m) in
the presence of a catalytic amount of KOt-Bu in solvent
free conditions. In addition, the antibacterial and antifungal
in vitro properties were tested against some human path-
ogenic microorganisms by employing the disk diffusion
technique. A majority of compounds were remarkably
active against several of the microorganisms. Compound 3i
was determined to be the most active compound.
synthesis of medicinally important compounds (Kumar
et al., 1991). Thiol nucleophilic reagents are also known to
show chemical reactivity toward chalcones, chalcon
epoxides, chalcone dibromides, and their corresponding
propynones. Conjugate addition of sulfur-centered nucle-
ophiles to a,b-unsaturated carbonyls such as chalcones
serves as a powerful synthetic method in this area of sulfur
chemistry (Garg et al., 2005; Sasai et al., 1995; Lee et al.,
2001; Cheng and Cromer, 2002).
A large number of reports are available on the inhibitory
effect of chalcone derivatives (Awasthi et al., 2009;
Siddiqui et al., 2008; Gopalakrishnan et al., 2009) on
enzymes and their bacteriostatic activity (Elba, 2000). As
already sulfur-containing compounds are known for their
diverse pharmacologic actions, the compounds were also
screened for antibacterial activity (Bhat and Singh, 1988).
Furthermore, some sulfur-containing compounds were
found to be antifungal and anticancer agents (Tandon et al.,
2004). In addition, there are numerous reports on the
antifungal, antimicrobial, antiatherosclerotic (Apitz-Castro
et al., 1983), hypocholesterolemic, hyperlipidemic (Bordia
et al., 1975) anti-thrombotic, antioxidant and anti-diabetic
effects (Sheela and Augusti, 1992) of sulfur compounds.
The target compounds, 3a–m, were synthesized as
depicted in Scheme 1.
Keywords Thiophenol Á Chalcones Á
Antimicrobial activity
Introduction
The preparation of sulfur-containing molecules has long
been a mainstay of organic synthesis because of their broad
application to organic and medicinal chemistry (Li et al.,
2006). The thio-Michael addition reaction has emerged as
one of the most powerful tools for C–S bond formation
(Fujita and Nagao, 1977). Thio-Michael addition provides
a widespread synthetic utility in organic chemistry (i) for
chemo-selective protection of olefinic double band in
unsaturated carbonyl compounds, (Trost and Keeley,
1975), (ii) for the generation of acyl vinyl cation equiva-
lents (Bakuzia and Bakuzis, 1981), and (iii) for the
Results and discussion
M. Ceylan (&) Á M. B. Gu¨rdere Á H. Gezegen
Department of Chemistry, Faculty of Arts and Sciences,
Gaziosmanpasa University, 60110 Tokat, Turkey
e-mail: mceylan@gop.edu.tr
Chemistry
In this study, a series of novel chalcone derivatives con-
taining thiophenol (3a–m) were prepared by the addition of
thiophenol to chalcones (1a–m). The reaction of chalcones
1a–m with thiophenol in the presence of a catalytic amount
˙
I. Karaman
Department of Biology, Faculty of Arts and Sciences,
Gaziosmanpasa University, 60250 Tokat, Turkey
123

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Med Chem Res (2011) 20:109–115
Ph
O
O
S
O
SH
O
i
+
X
X
1a-m
3a-m
2
Scheme 1 Schematic representation of the synthesized compounds.
3a: X = o-OCH3, 3b: X = m-OCH3, 3c: X = p-OCH3, 3d: X =
o-Cl, 3e: X = m-Cl, 3f: X = p-Cl, 3g: X = o-Br, 3h: X = m-Br, 3ı:
X = p-Br, 3i: X = o-OH, 3j: X = p-OH, 3k: X = o-NO2, 3l: X =
m-NO2, 3m: X = p-NO2. i = reagents and conditions: 6 % mol KOt-Bu,
r.t., 3h
(% 6 mol) of KOt-Bu at room temperature for 3 h gave
solely the products (3a–m) of 1,4-addition of thiophenol in
good yields. When this reaction was employed in a solvent
like CHCl3 and CH2Cl2, the reaction took a longer time
(36 h) and resulted in low yields.
1213 and Candida utilis KUEN 1031), five gram-positive
bacteria (Proteus Vulgaris KUEN 1329, Bacillus cereus
DSM 4312, Bacillus subtilis ATCC 6633, Staphylococcus
aureus ATCC 29213, Streptococcus Pyogenes ATCC 176),
and four gram-negative bacteria (Escherichia coli 111,
Pseudomonas aeruginosa ATCC 9027, Salmonella enteri-
dis ATCC 13076, and Pseudomonas aeruginosa ATCC
27859) were selected to evaluate the effectiveness of the
test compounds (3a–j) (Table 1).
The crude products were purified on a short silica gel col-
umn, which was followed by crystallization from CHCl3 /n-
hexane (3:7), and chalcone derivatives (1a–m) were obtained
in yields of 73–96%. All synthesized compounds (3a–m) are
novel compounds according to our literature survey.
The structures of the synthesized compounds 3a–
m were identified on the basis of Fourier-transform infrared
(FTIR) spectroscopy, 1H nuclear magnetic resonance
(NMR), and elemental analysis. Spectral values support the
expected structures.
A comparison of the compounds’ activity with that of
standard antibiotic SCF is effectively presented in Table 1.
All compounds except 3c demonstrated significant activity
against P. vulgaris, while 3i has the same activity as SCF.
Compound 3i showed remarkable activity against B. cer-
eus, B. subtilis and St. pyogenes, whereas the other com-
pounds displayed moderate and very low activity.
Compounds 3a, 3b, 3d, 3e, 3g, 3h, and 3i demonstrated a
significant level of activity against S. aureus. Compounds
3a and 3b showed moderate activity against E. coli, while
the other compounds showed very low activity or no
Antimicrobial activity
The synthesized compounds 3a–j underwent general anti-
microbial screening. Two yeasts (Candida albicans ATCC
Table 1 Antimicrobial activity of thiophenol derivatives (3a–j) (105 lg/disc) against the bacterial strains and Candida sp. isolates using the disc
diffusion method
3a
3b
3c
3d
3e
3f
3g
3h
3ı
3i
3j
SCF
MeOH
Gram-positive bacteria
P. vulgaris KUEN 1329
B. cereus DSM 4312
B. subtilis ATCC 6633
S. aureus ATCC 29213
St. pyogenes ATCC 176
Gram-negative bacteria
E. coli 111
15
10
14
17
15
14
–
–
–
16
11
15
18
–
17
11
14
16
14
14
10
–
16
12
15
17
13
15
13
–
15
–
18
15
17
16
17
17
–
18
26
23
22
19
13
9
12
–
–
–
–
11
11
12
–
–
16
–
–
–
–
13
13
–
–
13
15
18
15
14
–
10
13
–
–
14
18
14
–
15
19
16
10
15
17
–
10
15
15
16
–
16
16
–
–
15
17
–
–
14
19
17
10
14
17
–
20
22
23
16
9
10
12
12
P. aeruginosa ATCC 9027
S. enteridis ATCC 13076
P. aeruginosa ATCC 27859
Yeasts
17
–
–
C. albicans ATCC 1213
C. utilis KUEN 1031
17
17
12
12
16
17
14
14
17
16
11
21
20
23
22
6
14
13
13
15
15
14
13
15
13
10
Bold values show significant antimicrobial activity when compared with that of the standard antibiotic
SCF sulbactam (30 lg) ? cefoperazona (75 lg) = positive control
MeOH methanol = negative control
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Med Chem Res (2011) 20:109–115
111
activity. All compounds except 3b showed moderate
activity against P. aeruginosa ATCC 9027. All compounds
except 3c were found to display significant activity against
S. enteridis. Compound 3i was more active than SCF
against P. aeruginosa ATCC 27859, while 3e and 3g
showed the same activity as SCF, and compounds 3a and
3d showed significant activity. The compounds other than
3c, 3f, and 3ı demonstrated significant levels of activity
against yeast strain C. albinas. All compounds showed
moderate activity against C. utilis. As a result, it could be
argued that the most active compound is 3i according to the
disc diffusion method.
activity than positive controls. Compounds 3a, 3d, 3e, 3g,
3h, 3i and 3j showed better activity (MIC: 7.81–31.25 lg/
ml) than positive controls against S. aureus. Only com-
pound 3i showed the same activity (MIC: 3.9 lg/ml) as
positive controls against St. pyogenes. Compounds 3a, 3b,
3c, 3f, 3g, 3i, and 3j showed better activity (MIC:
15.62–62.5 lg/ml) than positive controls against E. coli,
while others showed lower activity. Compounds 3e and 3h
demonstrated the same activity (MIC: 15.62 lg/ml as CEF
against P. aeruginosa ATCC 9027, while other compounds
showed lower activity than positive controls. All com-
pounds except 3c and 3g showed lower activity than CS-T
against S. enteridis, while they demonstrated better activity
(MIC: 15.62–62.5 lg/ml) than CEF and AMP. Except 3f
and 3h, other compounds demonstrated better activity
(MIC: 31.25–125 lg/ml) than standard against P. aeru-
ginosa ATCC 27859. Compounds 3c, 3g and 3h showed
lower activity (MIC: [125 lg/ml) than standard against
C. albinas, while the others demonstrated better activity
(MIC: 15.62–125 lg/ml) than standard. Compounds 3b,
3e, and 3i showed better activity (MIC: 7.81–15.62 lg/ml)
against C. utilis, while the others have lower activity (MIC:
C125–62.5 lg/ml) than standard (MIC: 7.81–15.62 lg/
ml).
Among the synthesized compounds, 3a–j were sub-
jected to MIC (minimum inhibitory concentrations) studies
and the results are given in Table 2. Tetracycline, ceftri-
axone, and amphicilin were chosen as positive control.
MIC values were determined by serial microdilution
technique in Mueller–Hinton Broth for antibacterial assay
and in Sabouraud Dextrose Broth for antifungal assay.
As seen in the Table 2, while all compounds showed
lower activity than positive controls against P. vulgaris, 3i
showed the same activity (MIC: 15.62 lg/ml as CEF and
AMP. Moreover, 3f, 3i, and 3j demonstrated better activity
(MIC: 7.81 lg/ml) than CEF and AMP. Compounds 3a, 3c
and 3ı showed the same activity (MIC: 62.5 lg/ml) against
B. cereus, while other compounds showed better activity
(MIC: 15.62–31.25 lg/ml) than positive controls. Com-
pound 3ı showed the same activity (MIC: 15.62 lg/ml) as
CS-T against B. subtilis while others demonstrated lower
Concerning SAR, compound 3i containing o-OH group
found to be the most active compound according to the
inhibition zone and MIC values. In addition, when the
effects of methoxy substituent on activity against micro-
organism were investigated, 4-methoxy derivative 3c
Table 2 Minimum-inhibitory concentrations (MIC, in mg/ml) of synthesized compounds (3a–j)
3a 3b 3c 3d 3e 3f 3g 3h 3ı 3i
3j
MeOH CS-T CEF
AMP
Gram-positive bacteria
P. vulgaris KUEN 1329
B. cereus DSM 4312
B. subtilis ATCC 6633
S. aureus ATCC 29213
St. pyogenes ATCC 176
Gram-negative bacteria
E. coli 111
31.25 31.25 62.5 31.25 31.25 7.81 62.5 31.25 15.62
7.81 7.81
–
3.9
62.5
15.62
15.62 15.62
31.25 62.5 62.5 31.25 31.25 31.25 31.25 31.25 62.5
15.62 31.25 –
–
–
31.25 62.5 125 31.25 31.25 –
31.25 31.25 31.25 15.62 31.25 –
7.81 15.62 15.62 31.25 –
31.25 7.81
3.9
–
–
7.81
–
–
7.81 31.25 –
–
125
3.9
–
31.25
7.81 –
15.62 31.25 125
–
3.9 7.81
–
3.9
3.9
62.5
31.25 62.5
–
–
62.5 62.5
–
–
15.62 62.5
–
–
–
–
125
3.9
7.81 125
–
–
P. aeruginosa ATCC 9027 31.25
–
62.5 31.25 15.62 –
15.62 15.62 62.5
62.5 125 62.5
–
–
15.62 31.25
–
62.5
31.25 62.5
62.5
15.62 7.81
S. enteridis ATCC 13076
15.62 62.5
62.5 125
–
31.25 62.5
–
–
P. aeruginosa ATCC
27859
–
31.25 –
31.25 125
–
–
Yeasts
C. albicans ATCC 1213
C. utilis KUEN 1031
125
125
15.62 –
15.62 15.62 62.5
15.62 62.5
–
–
–
–
15.62 125
7.81 125
15.62 –
62.5
125
–
–
15.62 125 125
–
15.62 15.62 7.81
Bold values show significant antimicrobial activity when compared with that of the standard antibiotic
CS-T tetracycline, CEF ceftriaxone, AMP amphiciline = positive control
MeOH methanol = negative control
–, [125 lg/ml
123

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Med Chem Res (2011) 20:109–115
showed lower activity than 2- and 3-methoxy derivatives
(3a and 3b). In addition, 4-choloro derivative 3f showed
lower activity than 2- and 3-choloro derivatives (3d and
3e). While 4-bromo derivative 3ı showed better activity
than 2- and 3-bromo derivatives against yeast strains, 2-
and 3-bromo derivatives (3g and 3h) demonstrated better
activity than 3i against bacteria.
110.2, 107.1, 55.5, 47.4, 41.8. IR: (KBr cm-1) 3073, 2942,
2838, 1673, 1596, 1484, 1465, 1436, 1288, 1243, 754, 692.
Anal. Cald for C20H18O3S: C, 70.98; H, 5.36; S, 9.47.
Found: C, 70.83; H, 5.12; S, 9.33.
3-(Furan–2-yl)-1-(3-methoxyphenyl)-3-(phenylthio)pro-
pan-1-one (3b): Brown oil, yield: 81%. 1H-NMR (400
MHz, CDCl3, ppm): d 7.54–7.12 (m, 10H, H2, H10, H11,
H12, H13, H14, H15, H17, H16, H18), 6.25 (dd, J = 3.2,
1.8 Hz, H3), 6.05 (d, J = 3.2 Hz, 1H, H4), 5.03 (dd, J = 7.7,
6.5 Hz, H6), 3.84 (s, 3H, –OCH3), 3.75 (dd, J = 17.3, 7.8
Hz, 1H, H7), 3.53 (dd, J = 17.3, 6.3 Hz, 1H, H7). 13C-
NMR (100 MHz, CDCl3, ppm): d 196.4, 159.9, 153.3,
141.9, 137.9, 133.8, 129.7, 128.9, 128.1, 120.7, 119.9,
112.3, 110.3, 107.4, 55.4, 42.1, 41.6. IR: (KBr cm-1) 3073,
3004, 2938, 2834, 1685, 1596, 1583, 1482, 1430, 1288,
1259, 1041, 1012, 786, 740, 692. Anal. Cald for
C20H18O3S: C, 70.98; H, 5.36; S, 9.47. Found: C, 70.83; H,
5.19; S, 9.33.
Experimental
Chemistry
Melting points were measured on Electrothermal 9100
apparatus. IR spectrums (KBr disc or CHCl3) were recor-
1
ded on a Jasco FT/IR-430 spectrometer. H and 13C NMR
spectra were recorded on a Bruker Avance DPX-400
instrument. As internal standards served TMS (d 0.00) for
1H NMR and CDCl3 (d 77.0) for 13C NMR spectroscopy
J values are given in Hz. The multiplicities of the signals in
the 1H NMR spectra are abbreviated by s (singlet), d
(doublet), t (triplet), q (quarted), m (multiplet), br (broad)
and combinations thereof. Elemental analyses were
obtained from a LECO CHNS 932 Elemental Analyzer. All
column chromatographies were performed on silica gel
(60-230 mesh, Merck).
3-(Furan–2-yl)-1-(4-methoxyphenyl)-3-(phenylthio)pro-
pan-1-one (3c): Yellow solid, yield: 95%, mp 64–67°C.
1H-NMR (400 MHz, CDCl3, ppm): d 7.93 (d, J = 8.9 Hz,
2H, AA’, H10, H13), 7.37–7.27 (m, 6H, H2, H14, H15,
H16, H17, H18), 6.95 (d, J = 8.9 Hz, 2H, XX’, H11, H12),
6.24 (dd, J = 3.2, 1.8 Hz, 1H, H3), 6.04 (d, J = 3.2 Hz, 1H,
H4), 5.02 (dd, J = 7.8, 6.3 Hz, 1H, H6), 3.87 (s, 3H), 3.67
(dd, J = 17.0, 7.9 Hz, 1H, H7), 3.51 (dd, J = 17.0, 6.3 Hz,
1H, H7). 13C-NMR (100 MHz, CDCl3): d 195.0, 163.7,
153.4, 141.9, 133.7, 133.4, 130.5, 129.7, 128.8, 128.0,
113.8, 110.3, 107.4, 55.5, 41.7, 41.6. IR: (KBr cm-1) 3421,
1675, 1600, 1509, 1438, 1419, 1261, 1172, 771, 750, 692.
Anal. Cald for C20H18O3S: C, 70.98; H, 5.36; S, 9.47.
Found: C, 70.84; H, 5.12; S, 9.41.
General procedure for the synthesis of 3a–3m
To a magnetically stirred mixture of chalcone derivative
(1 mmol) and thiophenol (2 and/or 3 mmol) was added a
catalytic amount of KOt-Bu (6% mol) and the reaction
mixture was stirred at room temperature for 3 h. Then, the
mixture was washed with dilute HCl and extracted with
CHCl3. The organic layer was dried over Na2SO4 and
removed the solvent in vacuum. The residue was purified
on a silica gel column, eluted with CHCl3/n-hexane (3:7)
and/or crystallized in CHCl3/n-hexane (3:7).
1-(2-Chlorophenyl)-3-(Furan-2-yl)-3-(phenylthio)pro-
pan-1-one (3d): Brown oil, yield: 87%. 1H-NMR (400
MHz, CDCl3): d 7.55–7.21 (m, 10H, H2, H10, H11, H12,
H13, H14, H15, H17, H16, H18), 6.26 (dd, J = 3.2, 1.8 Hz,
H3), 6.06 (d, J = 3.2 Hz, 1H, H4), 4.97 (t, J = 7.3 Hz, H6),
3.72 (dd, J = 17.2, 7.8 Hz, 1H, H7), 3.60 (dd, J = 17.2, 6.9
Hz, 1H, H7). 13C-NMR (100 MHz, CDCl3, ppm): d 199.5,
153.1, 142.0, 138.8, 133.9, 133.1, 132.1, 130.9, 130.5,
129.4, 129.2, 128.9, 128.2, 127.5, 127.2, 127.0, 110.4,
107.6, 46.4, 42.0. IR: (KBr cm-1) 3058, 1693, 1589, 1502,
1477, 1434, 1284, 1218, 1149, 1012, 771, 738, 690. Anal.
Cald for C19H15ClO2S: C, 66.56; H, 4.41; S, 9.35; Found:
66.40; H, 4.32; S, 9.23.
Data
3-(Furan–2-yl)-1-(2-methoxyphenyl)-3-(phenylthio)pro-
pan-1-one (3a): Brown oil, yield: 93%. 1H-NMR (400
MHz, CDCl3, ppm): d 7.68 (dd, J = 7.7, 1.8 Hz, 1H, H10),
7.48 (dd, J = 15.6, 1.8 Hz, 1H, H12), 7.48 (dd, J = 1.7, 1.1
Hz, 1H, H2), 7.37–7.33 (m, 2H, H14, H15), 7.30–7.26 (m,
2H, H17, H18), 7.02–6.95 (m, 2H, H11, H13), 6.23 (dd, J =
3.2, 1.8 Hz, H3), 6.01 (d, J = 3.2 Hz, 1H, H4), 4.96 (dd, J =
8.0, 6.5 Hz, H6), 3.99 (s, 3H, –OCH3), 3.77 (dd, J = 17.5,
8.1 Hz, 1H, H7), 3.58 (dd, J = 17.5, 6.4 Hz, 1H, H7). 13C-
NMR (100 MHz, CDCl3, ppm): d 198.6, 158.6, 153.8,
141.8, 133.9, 133.8, 130.6, 128.7, 127.9, 120.7, 111.5,
1-(3-Chlorophenyl)-3-(Furan-2-yl)-3-(phenylthio)pro-
pan-1-one (3e): Brown oil, yield: 90%. 1H-NMR (400
MHz, CDCl3, ppm): d 7.90 (t, J = 1.7 Hz, 1H, H14), 7.81
(dt, J = 7.8, 1.1 Hz, 1H, H10), 7.57–7.41 (m, 2H, H11,
H12), 7.39–7.27 (m, 6H, H2, H14, H15, H17, H16, H18),
6.25 (dd, J = 3.2, 1.8 Hz, H3), 6.05 (d, J = 3.2 Hz, 1H, H4),
4.98 (dd, J = 7.6, 6.5 Hz, 1H, H6), 3.69 (dd, J = 17.3, 7.8
Hz, 1H, H7), 3.52 (dd, J = 17.3, 6.4 Hz, 1H, H7).
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Med Chem Res (2011) 20:109–115
113
13C-NMR (100 MHz, CDCl3, ppm): d 195.4, 153.1, 142.0,
138.1, 133.8, 133.3, 130.0, 129.1, 128.9, 128.2, 128.1,
127.4, 127.1, 126.2, 110.3, 107.5, 42.1, 41.6. IR: (KBr
cm-1) 3062, 2923, 2852, 1689, 1600, 1571, 1477, 1438,
1423, 1284, 1220, 1014, 786, 738, 690. Anal. Cald for
C19H15ClO2S: C, 66.56; H, 4.41; S, 9.35. Found: 66.50; H,
4.22; S, 9.28.
7.5, 6.7 Hz, 1H, H6), 3.68 (dd, J = 17.2, 7.8 Hz, 1H, H7),
3.51 (dd, J = 17.3, 6.4 Hz, 1H, H7). 13C-NMR (75 MHz,
CDCl3, ppm): d 195.6, 153.1, 142.0, 135.3, 133.8, 133.1,
132.0, 129.6, 128.9, 128.7, 128.1, 127.4, 110.3, 107.4,
41.9, 41.6. IR: (KBr cm-1) 3446, 3058, 2972, 1685, 1601,
1585, 1562, 1477, 1228, 1070, 1008, 741, 690. Anal. Cald
for C19H15BrO2S: C, 58.92; H, 3.90; S, 8.28. Found: C,
58.84; H, 3.81; S, 8.11.
1-(4-Chlorophenyl)-3-(Furan-2-yl)-3-(phenylthio)pro-
pan-1-one (3f): Yellow solid, yield: 90%, mp 74–76°C. 1H-
NMR (400 MHz, CDCl3, ppm): d 7.74 (d, J = 13.4 Hz, 2H,
AA’, H10, H13), 7.30 (d, J = 13.4 Hz, 2H, XX’, H11,
H12), 7.25–7.14 (m, 6H, H2, H14, H15, H16, H17, H18),
6.12 (dd, J = 3.2, 1.8 Hz, 1H, H3), 5.93 (d, J = 3.2 Hz, 1H,
H4), 4.88 (dd, J = 7.6, 6.5 Hz, 1H, H6), 3.56 (dd, J = 17.2,
7.8 Hz, 1H, H7), 3.40 (dd, J = 17.2, 6.4 Hz, 1H, H7). 13C-
NMR (100 MHz, CDCl3): d 195.4, 153.2, 142.0, 139.8,
134.8, 133.8, 133.2, 129.6, 129.0, 128.9, 128.2, 110.4,
107.5, 42.0, 41.6. IR: (KBr cm-1) 3361, 3058, 2904, 1687,
1589, 1400, 1224, 1093, 938, 819, 692. Anal. Cald for
C19H15ClO2S: C, 66.56; H, 4.41; S, 9.35. Found: 66.53; H,
4.38; S, 9.30.
3-(Furan–2-yl)-1-(2-hydroxyphenyl)-3-(phenylthio)pro-
pan–1-one (3i): Brown oil, yield: 88%. 1H-NMR (300
MHz, CDCl3, ppm): d 12.10 (s, 1H, OH), 7.75 (dd, J = 8.1,
1.5 Hz, 1H, H10), 7.54–7.47 (m, 1H, H2, H13), 7.39–7.29
(m, 2H, H14, H15, H16, H17, H18), 7.02–6.98 (m, 2H,
H11–H12), 6.27 (dd, J = 3.2, 1.9 Hz, H3), 6.06 (d, J = 3.2
Hz, 1H, H4), 4.98 (dd, J = 7.7, 6.4 Hz, H6), 3.75 (dd, J =
17.3, 7.8 Hz, 1H, H7), 3.39 (dd, J = 17.3, 6.3 Hz, 1H, H7).
13C-NMR (75 MHz, CDCl3, ppm): d 202.4, 162.5, 152.9,
142.1, 136.7, 133.9, 132.9, 129.1, 129.0, 128.9, 128.2,
127.4, 119.2, 119.0, 110.4, 107.5, 41.5, 41.4. IR: (KBr
cm-1) 3141, 3124, 2372, 2343, 1639, 1581, 1552, 1214,
1159, 1016, 968, 744, 651. Anal. Cald for C19H16O3S: C,
70.35; H, 4.97; S, 9.88. Found: C, 70.13; H, 4.86; S, 9.72.
3-(Furan–2-yl)-1-(4-hydroxyphenyl)-3-(phenylthio)pro-
pan–1-one (3j): Yellow solid, yield: 95%, mp 98–102°C.
1H-NMR (300 MHz, CDCl3, ppm): d 7.87 (d, J = 8.4 Hz,
2H, AA’, H10, H14), 7.36–7.26 (m, 6H, H2, H14, H15,
H16, H17, H18), 6.89 (d, J = 8.4 Hz, 2H, XX’, H11, H12),
6.24–6.22 (m, 1H, H3), 6.02 (d, J = 3.2 Hz, 1H, H4), 4.98
(t, J = 7.1 Hz, 1H, H6), 3.68 (dd, J = 17.0, 7.9 Hz, 1H, H7),
3.51 (dd, J = 17.0, 6.3 Hz, 1H, H7). 13C-NMR (75 MHz,
CDCl3, ppm): d 195.9, 160.8, 153.2, 141.9, 133.7, 133.1,
130.9, 129.47, 129.0, 128.8, 128.0, 127.5, 115.5, 110.3,
107.4, 41.8, 41.6. IR: (KBr cm-1) 3211, 3119, 2362, 2338,
1648, 1604, 1589, 1514, 1234, 1171, 1014, 959, 740, 690.
Anal. Cald for C19H16O3S : C, 70.35; H, 4.97; S, 9.88.
Found: C, 70.25; H, 4.91; S, 9.83.
1-(2-Bromophenyl)-3-(furan-2-yl)-3-(phenylthio)pro-
pan-1-one (3g): Brown oil, yield: 73%. 1H-NMR (400
MHz, CDCl3, ppm): d = 7.51–7.13 (m, 10H, H2, H10, H11,
H12, H13, H14, H15, H17, H16, H18), 6.11 (dd, J = 3.2,
1.8 Hz, H3), 5.90 (d, J = 3.2 Hz, 1H, H4), 4.77 (t, J = 7.3
Hz, H6), 3.53 (J = 17.2, 7.9 Hz, 1H, H7), 3.41 (J = 17.2, 6.8
Hz, 1H, H7). 13C-NMR (100 MHz, CDCl3, ppm): d 196.3,
153.0, 142.0, 138.3, 136.2, 133.8, 133.1, 131.2, 130.2,
129.0, 128.9, 128.1, 127.5, 127.1, 126.6, 123.0, 110.4,
107.5, 42.1, 41.6. IR: (KBr cm-1) 3118, 3058, 2923, 1700,
1600, 1587, 1301, 1282, 1220, 1012, 754, 738, 690. Anal.
Cald for C19H15BrO2S: C, 58.92; H, 3.90; S, 8.28. Found:
C, 58.86; H, 3.71; S, 8.19.
1-(3-Bromophenyl)-3-(furan-2-yl)-3-(phenylthio)pro-
pan-1-one (3h): Brown oil, yield: 83%. 1H-NMR (400
MHz, CDCl3, ppm): d 7.27–7.13 (m, 10H, H2, H10, H11,
H12, H13, H14, H15, H17, H16, H18), 6.12 (dd, J = 3.1,
1.9 Hz, H3), 5.93 (d, J = 3.2 Hz, 1H, H4), 4.85 (t, J = 6.7
Hz, H6), 3.55 (dd, J = 17.3, 7.8 Hz, 1H, H7), 3.39 (dd, J =
16.7, 6.4 Hz, 1H, H7). 13C-NMR (100 MHz, CDCl3, ppm):
d 195.3, 153.4, 142.0, 138.3, 136.2, 133.8, 133.1, 131.2,
130.2, 128.9, 128.1, 126.6, 123.1, 110.4, 107.5, 42.1, 41.6.
IR: (KBr cm-1) 3367, 3118, 3062, 3018, 2923, 1691, 1600,
1565, 1477, 1421, 1220, 1014, 786, 746, 692. Anal. Cald
for C19H15BrO2S: C, 58.92; H, 3.90; S, 8.28. Found: C,
58.82; H, 3.78; S, 8.14.
3-(Furan–2-yl)-1-(2-nitrophenyl)-3-(phenylthio)propan–
1
1-one (3k): Brown oil, yield: 73%. H-NMR (400 MHz,
CDCl3, ppm): d 8.11–8.08 (m, 1H, H13), 7.71–7.68 (m,
1H, H10), 7.54–7.45 (m, 2H, H11, H12), 7.35–7.22 (m, 2H,
H2, H14, H15, H16, H17, H18), 6.27 (dd, J = 3.2, 2.0 Hz,
H3), 6.06 (d, J = 3.2 Hz, 1H, H4), 4.90 (t, J = 8.0 Hz, H6),
3.59 (dd, J = 17.2, 8.0 Hz, 1H, H7), 3.46 (dd, J = 17.2, 6.4
Hz, 1H, H7). 13C-NMR (100 MHz, CDCl3, ppm): d 199.2,
152.6, 142.0, 137.4, 137.0, 134.2, 133.7, 130.7, 129.1,
128.9, 128.2, 127.6, 127.4, 127.2, 124.3, 110.4, 107.8,
46.1, 41.6. IR: (KBr cm-1) 3648, 3088, 2863, 1693, 1634,
1561, 1487, 1416, 1223, 1030, 1010, 748, 674. Anal. Cald
for C19H15NO4S: C, 64.58; H, 4.28; N, 3.96; S, 9.07.
Found: C, 63.40; H, 4.12; N, 3.76; 9.01.
1-(4-Bromophenyl)-3-(furan-2-yl)-3-(phenylthio)pro-
pan-1-one (3ı): Brown oil, yield: 96%. 1H-NMR (300
MHz, CDCl3, ppm): d 7.82 (d, J = 8.6 Hz, 2H, AA’, H10,
H13), 7.63 (d, J = 8.6 Hz, 2H, XX’, H11, H12), 7.40–7.28
(m, 6H, H2, H14, H15, H16, H17, H18), 6.25 (dd, J = 3.1,
1.9 Hz, 1H, H3), 6.03 (d, J = 3.2 Hz, 1H, H4), 4.98 (dd, J =
3-(Furan–2-yl)-1-(3-nitrophenyl)-3-(phenylthio)propan–
1
1-one (3l): Brown oil, yield: 79%. H-NMR (400 MHz,
CDCl3, ppm): d 8.72 (t, J = 1.9 Hz, H14), 8.43–8.38 (m,
123

114
Med Chem Res (2011) 20:109–115
1H, H12), 8.23 (dt, J = 7.8, 1.1 Hz, 1H, H10), 7.65 (t, J =
7.9 Hz, H11), 7.38–7.28 (m, 6H, H2, H14, H15, H16, H17,
H18), 6.24 (dd, J = 3.3, 1.8 Hz, H3), 6.07 (d, J = 3.2 Hz,
1H, H4), 4.98 (t, J = 7.0 Hz, H6), 3.75 (dd, J = 17.3, 7.6
Hz, 1H, H7), 3.59 (dd, J = 17.3, 6.4 Hz, 1H, H7). 13C-
NMR (100 MHz, CDCl3, ppm): d 194.7, 152.7, 148.4,
142.1, 137.9, 133.8, 133.6, 132.9, 130.0, 129.1, 128.3,
127.6, 127.4, 127.1, 123.0, 110.4, 107.6, 42.3, 41.5. IR:
(KBr cm-1) 3445, 3080, 2923, 2852, 1697, 1614, 1531,
1477, 1438, 1348, 1223, 1087, 1014, 738, 691. Anal. Cald
for C19H15NO4S: C, 64.58; H, 4.28; N, 3.96; S, 9.07.
Found: C, 64.34; H, 4.21; N, 3.88; S, 8.99.
used as positive reference standard to determine the sen-
sitivity of a strain for each microbial species tested. The
inoculated plates were incubated at 36°C for 24 h for
clinical bacterial strains, 48 h for yeast, and 72 h for fungal
strains. Antimicrobial activity was evaluated by measuring
the zone of inhibition against the test organisms. Each
assay in this experiment was repeated twice.
Microdilution assay
The minimum inhibitory concentration (MIC) values were
also studied for the microorganisms, which were deter-
mined to be sensitive to the substances tested in the disc
diffusion assay. Inocula of microorganisms were prepared
using 12-h broth cultures, and suspensions were adjusted to
0.5 McFarland standard turbidity. Each substance dissolved
in methanol was first diluted to the highest concentration
(500 lg/ml) to be tested, and then serial twofold dilutions
were made in a concentration range of 3.9–500 lg/ml in
10-ml sterile test tubes containing nutrient broth. This
process was also repeated for the antibiotic and methanol.
MIC values of the compounds against bacterial strains and
Candida sp. isolates were determined on the basis of a
micro-well dilution method (Zgoda and Porter 2001). 112-
well plates were prepared by dispensing into each well
75 ll of nutrient broth and 5 ll of the inoculums. 75 ll of
chalcone derivative to be tested initially was prepared at a
concentration of 500 lg/ml and was added into the first
wells. Then, 75 ll of their serial dilutions was transferred
into eight consecutive wells. The last well containing
150 ll of nutrient broth without compound and 5 ll of the
inoculums on each strip was used as negative control.
Tetracycline, ceftriaxone, and amphicilin (antibiotics) at a
concentration range of 500–3.9 lg/ml was prepared in
nutrient broth and used as standard drug for positive con-
trol. The final volume in each well was 155 ll. The 112-
well plates were incubated at 36°C for 24 h. The MIC
results were repeated at least twice.
3-(Furan–2-yl)-1-(4-nitrophenyl)-3-(phenylthio)propan-
1
1-one (3m): Brown oil, yield: 85%. H-NMR (400 MHz,
CDCl3, ppm): d 8.25 (d, J = 8.7 Hz, 2H, AA’, H10, H13),
8.03 (d, J = 8.7 Hz, 2H, XX’, H11, H12), 7.35–7.25 (m,
6H, H2, H14, H15, H16, H17, H18), 6.24 (dd, J = 3.1, 1.9
Hz, 1H, H3), 6.07 (d, J = 3.1 Hz, 1H, H4), 4.98 (t, J = 7.0
Hz, 1H, H6), 3.75 (dd, J = 17.5, 7.6 Hz, 1H, H7), 3.60 (dd,
J = 17.5, 6.4 Hz, 1H, H7). 13C-NMR (100 MHz, CDCl3,
ppm): d 195.3, 152.9, 150.4, 142.1, 140.8, 136.9, 133.8,
133.0, 129.1, 129.0, 128.3, 127.4, 127.2, 123.9, 110.5,
107.6, 42.6, 41.5. IR: (KBr cm-1) 3111, 3073, 3019, 2907,
2857, 1886, 1696, 1525, 1344, 1319, 1207, 1012, 854, 740,
691. Anal. Cald for C19H15NO4S: C, 64.58; H, 4.28; N,
3.96; S, 9.07. Found: C, 64.40; H, 4.16; N, 3.55; S, 9.03.
Microbiology
Preparation of microorganisms
A total of 11 microbial cultures belonging to nine bacterial
and two fungal species were used in this study (Table 1).
The cultures were grown in Mueller–Hinton Broth (Merck)
for all the bacterial strains for 24 h of incubation at 36°C.
C. albicans and C. utilis were grown in Sabouraud Dex-
trose Broth (Merck) in incubation for 24 h at 25°C.
Disc diffusion assay
Conclusion
Antimicrobial tests were carried out by disk diffusion
method (Karaman et al., 2003; Murray et al., 1995) using
100 ll of suspension containing 108 CFU/ml of bacteria
and 106 CFU/ml of yeast spread on Nutrient Agar (NA),
Sabouraud Dextrose Agar (SDA) and Potato Dextrose Agar
(PDA) medium, respectively. The blank discs (Oxoid =
6 mm in diameter) were impregnated with 20 ll of each
substance (105 lg/disc) and placed on inoculated agar.
Negative controls were prepared using the same solvents
(Methanol) employed to dissolve each substance. Sulbac-
tam (30 lg) ? Cefoperazona (75 lg) (105 lg/disc) was
In conclusion, a novel series of 14 thiophenol derivatives
(3a–m) were prepared by the addition of thiophenol to
chalcones (1a–m) in the presence of potassium-tertiary-
butoxide (KOt-Bu) in solvent free conditions. Among these
compounds, the biological activities of 3a–j were screened
against 11 different human pathogenic microorganisms.
The majority of the compounds were found to be active.
Acknowledgments The authors are indebted to the Technical
Research Council of Turkey (Grant TUBITAK-106T103) for finan-
cial support of this work.
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Res 18:341–350
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