Synthesis and screening antimicrobial activities of novel 1,3-diaryl-3-(phenylthio)propan-1-one derivatives

Article abstract of DOI:10.1080/10426507.2011.632387

In this study, a series of novel β-mercapto carbonyl derivatives (3a-j) was prepared by addition of thiophenol (2) to chalcones (1a-j) in the presence of catalytic amount of iodine (10 mol%) in CH₂Cl ₂. Antibacterial and antifungal in vitro properties of the synthesized compounds were tested against some human pathogenic microorganisms by employing the disk diffusion technique. For the most active compounds, also minimum inhibitory concentrations (MICs) were determined. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Full text of DOI:10.1080/10426507.2011.632387

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Synthesis and Screening Antimicrobial
Activities of Novel 1,3-Diaryl-3-
(Phenylthio)Propan-1-One Derivatives
İsa Karaman a , Hayreddin Gezegen b , Mustafa Ceylan b & Merve
Dilmaç a
a Department of Biology, Faculty of Arts and Sciences,
Gaziosmanpasa University, Tokat, Turkey
b Department of Chemistry, Faculty of Arts and Sciences,
Gaziosmanpasa University, Tokat, Turkey
Published online: 27 Mar 2012.
To cite this article: İsa Karaman , Hayreddin Gezegen , Mustafa Ceylan & Merve Dilmaç (2012)
Synthesis and Screening Antimicrobial Activities of Novel 1,3-Diaryl-3- (Phenylthio)Propan-1-
One Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:5, 580-586, DOI:
10.1080/10426507.2011.632387
To link to this article: http://dx.doi.org/10.1080/10426507.2011.632387
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Phosphorus, Sulfur, and Silicon, 187:580–586, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.632387
SYNTHESIS AND SCREENING ANTIMICROBIAL
ACTIVITIES OF NOVEL 1,3-DIARYL-3-
(PHENYLTHIO)PROPAN-1-ONE DERIVATIVES
1
2
2
˙
Isa Karaman, Hayreddin Gezegen, Mustafa Ceylan,
and Merve Dilmac¸1
1Department of Biology, Faculty of Arts and Sciences, Gaziosmanpasa University,
Tokat, Turkey
2Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpasa
University, Tokat, Turkey
GRAPHICAL ABSTRACT
Ph
O
O
S
10% I2, CH2Cl2
25 oC
+
Ph SH
Ar
Ar'
Ar
Ar'
1a-j
2
3a-j
Ar' = Ph
Ar' = Ph
3a; Ar = o-OCH3−Ph
3b; Ar = Ph
3c; Ar = Ph
3f; Ar = o-NO2−Ph
3g; Ar = 2-Furyl
Ar' = o-CH3−Ph
Ar' = m-CH3−Ph
Ar' = Ph
Ar' = p-OCH3−Ph
Ar' = o-Cl−Ph
Ar' = 2-Thiophenyl
3h; Ar = 2-Furyl
3i; Ar = p-OCH3−Ph
3j; Ar = o-OH−Ph
3d; Ar = p-Cl−Ph
3e; Ar = Ph
Ar' = p-Cl−Ph
Ar' = 2-Thiophenyl
Abstract In this study, a series of novel β-mercapto carbonyl derivatives (3a–j) was prepared
by addition of thiophenol (2) to chalcones (1a–j) in the presence of catalytic amount of iodine
(10 mol%) in CH2Cl2. Antibacterial and antifungal in vitro properties of the synthesized
compounds were tested against some human pathogenic microorganisms by employing the disk
diffusion technique. For the most active compounds, also minimum inhibitory concentrations
(MICs) were determined.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Chalcone; thiophenol; Michael addition; antibacterial and antifungal activity
INTRODUCTION
The preparation of sulfur-containing molecules has long been a mainstay of or-
ganic synthesis because of their broad application to organic and medicinal chemistry.1
Sulfur-containing compounds are known to exhibit various biological activities, such as
Received 15 July 2011; accepted 12 October 2011.
The authors are indebted to the Technical Research Council of Turkey (Grant TUBITAK-106T103) for
financial support of this work.
˙
Address correspondence to Isa Karaman and Hayreddin Gezegen, Department of Biology, Faculty of
Arts and Sciences, Gaziosmanpasa University, 60250 Tokat, Turkey. E-mail: isa.karaman@gop.edu.tr; hayrettin.
gezegen@gop.edu.tr
580

SYNTHESIS AND SCREENING ANTIMICROBIAL ACTIVITIES
581
antibacterial,2–4 antimicrobial,5,6 antifungal,7,8 anticancer,9,10 antithrombotic, antioxidant,
antidiabetic effects,11 and as potential cytotoxic agent.12 Thia-Michael addition reaction is
one of the most fundamental C–S bond-forming reactions in the synthesis of β-mercapto
carbonyl derivatives, which have valuable synthetic scaffolds for biological, medicinal,
and synthetic organic chemists.13–16 They are used for the synthesis of various biologically
active compounds such as thiochromans,17,18 thiapyrans,19 benzothiazapines,20–23 and 4,5-
dihydropyrazoles.24 On the other hand, chalcones, either natural or synthetic, are known
to exhibit various biological activities25 such as antioxidant,26 antileishmanial activity,27
antihyperglycemic activity,28 antimicrobial activity29 among others. In addition, chalcones
are very important compounds as a Michael acceptor in organic syntheses. Conjugate addi-
tion of sulfur-centered nucleophiles to α,β-unsaturated carbonyls such as chalcones serves
a powerful synthetic method in this area of sulfur chemistry.30–32 Traditionally, the 1,4-
addition of thiols is catalyzed by strong bases such as alkali metal alkoxides, hydroxides,
and amines.33,34 But in recent years, molecular iodine has been used as a useful catalyst for
1,4-addition of thiols and indoles to enones.35–37
This study reports the addition of thiophenol to chalcones in the mild conditions in the
presence of catalytic amount of molecular iodine. This reaction occurs in short reaction time
at room temperature and result in high yield.14,38 In additional, the antimicrobial activities
of the 1,3-diaryl-3-(phenylthio)propan-1-one derivatives (3a–j) were investigated against
the 10 different human pathogen microorganisms.
RESULTS AND DISCUSSION
The addition of thiophenol with chalcone was explored in order to search for the
optimal conditions, such as catalysts and solvent. The reaction did not take place when it
was carried out separately in ethanol or methanol with solid I2 and ethanol or methanol
with NaOH. A longer reaction time would be necessary and lower yield was obtained with
CH2Cl2 and solid I2. The best results were obtained using CH2Cl2 and dissolved I2 in
CH2Cl2 for about 3 h.
Treatment of chalcone derivatives (1a–j) with thiophenol (2) and a solution
of 10 mol% iodine in CH2Cl2 at room temperature for 3 h yielded 1,3-diaryl-3-
(phenylthio)propan-1-one derivatives (3a–j) (Scheme 1), which were purified by silica gel
column and crystallization. The final yield of the obtained derivatives was in the range
1
of 74%–94% (Table 1). The compounds (3a–j) have been characterized by IR, H and
Ph
O
O
S
10% I2, CH2Cl2
25 oC
+
Ph SH
Ar
Ar'
Ar
Ar'
1a--j
2
3a--j
Ar' = Ph
Ar' = Ph
3a; Ar = o-OCH3−Ph
3b; Ar = Ph
3c; Ar = Ph
3f; Ar = o-NO2−Ph
3g; Ar = 2-Furyl
Ar' = o-CH3−Ph
Ar' = m-CH3−Ph
Ar' = Ph
Ar' = p-OCH3−Ph
Ar' = o-Cl−Ph
Ar' = 2-Thiophenyl
3h; Ar = 2-Furyl
3i; Ar = p-OCH3−Ph
3j; Ar = o-OH−Ph
3d; Ar = p-Cl−Ph
3e; Ar = Ph
Ar' = p-Cl−Ph
Ar' = 2-Thiophenyl
Scheme 1

˙
582
I. KARAMAN ET AL.
1
13C NMR, and elemental analyze data. In the H NMR spectrum of 3a–j, the protons of
PhCOCH2 led to an AB system that is characteristic to these compounds;39 part A of the
AB system was shown as a doublet of doublet at δ = 3.80–3.52 (J = 17.4–16.4, 8.6–7.0
Hz) and that of part B as a doublet of doublet at δ = 3.66–3.47 (J = 17.4–16.4, 7.6–5.8
1
Hz). Moreover, in the H NMR spectrum of 3a–j the protons of PhCOCH2CH led to a
doublet of doublet at δ = 5.42–4.89 (J = 8.4–8.0, 6.6–5.6 Hz). All of the spectral data are
consistent with the proposed compounds.
Comparison of activity of the compounds with the standard antibiotic SCF is pre-
sented in Table S1 (Supplemental Materials). Compounds 3f, 3h, and 3j have significantly
and/or remarkable activity against Proteus vulgaris KUEN 1329, Candida utilis KUEN
1031, Bacillus cereus DSM 4312, Salmonella enteridis ATCC 13076, and Candida albi-
cans ATCC 1213. Compounds 3a, 3d, and 3i showed moderate activity against Escherichia
coli 111 while the other compounds showed very low activity or not activity. Only com-
pounds 3j showed significantly activity against Bacillus cereus DSM 4312. All compounds
demonstrated low activity against Pseudomonas aeruginosa ATCC 9027, Bacillus subtilis
ATCC 6633, and Staphylococcus aureus ATCC 29213.
As seen in Table S2 (Supplemental Materials), most of the compounds showed lower
activity than positive controls against Proteus vulgaris KUEN 1329, Candida utilis KUEN
1031, Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 29213, and
Streptococcus pyogenes ATCC 176. Compound 3i demonstrated low activity than CEF and
AMP against Escherichia coli 111, better than (MIC: 250 µg/mL) AMP against Bacillus
subtilis ATCC 6633. Compound 3j showed the same activity (MIC: 7.8 µg/mL) with the
Cs-T, better than CEF (MIC: 125 µg/mL) and AMP (MIC: 500 µg/mL) against Salmonella
enteridis ATCC 13076.
Concerning SAR, compound 3i (4-OCH3 on Arꢁ ring; Ar = 2-thiophenyl) and 3j
(2-OH on Arꢁ ring; Ar = 2-thiophenyl) found to be the most active compounds according to
the MIC values. In addition, when the effects of methoxy and nitro substituent on activity
were discussed. Compound 3f (2-NO2 on Arꢁ ring) showed better activity than 3a (2-OCH3
on Arꢁ ring). Moreover, compound 3h (Arꢁ = 2-furan; 2-Cl on Ar ring) showed better
activity than 3g (Arꢁ = 2-furan; 4-OCH3 on Ar ring) according to the inhibition zones.
According to the results, compounds, containing hydroxyl group and furan ring, show
remarkable antibacterial activity.
Table 1 Synthesized 1,3-diaryl-3-(phenylthio)propan-1-one derivatives
Products
Ar
Arꢁ
Yield (%)
mp (◦C)
3a
3b
3c
3d
3e
3f
3g
3h
3i
o-OCH3–Ph
Ph
Ph
p-Cl–Ph
Ph
o-N02–Ph
2-Furyl
2-Furyl
p-OCH3–Ph
o-OH–Ph
Ph
88
88
82
91
94
74
84
82
91
89
86–88
85–87
54–56
94–97
88–90
57–59
94–96
77–79
72–74
77–79
o-CH3–Ph
m-CH3–Ph
Ph
p-Cl–Ph
Ph
p-OCH3–Ph
o-Cl–Ph
2-Thiophenyl
2-Thiophenyl
3j

SYNTHESIS AND SCREENING ANTIMICROBIAL ACTIVITIES
583
Summary, a series of β-mercapto carbonyl derivatives (3a–j) were prepared by iodine-
catalyzed addition of thiophenol (2) to chalcones (1a–j) at room temperature for 3 h. The
most active compounds are 3i,j.
EXPERIMENTAL
Chemistry
Melting points were measured on Electrothermal 9100 apparatus. IR spectrums (KCl
1
disc) were recorded 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 (δ
1
0.00) for H NMR and CDCl3 (δ 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). Anhydrous
sodium sulfate was used as a drying agent for the organic phase.
Synthesis of chalcone derivatives (1a–j) were carried out through Claisen–Schmidt
condensation29 of substituted acetophenones and 2-furyl methyl ketone with the substituted
benzaldehydes and thiophene-2-carbaldehyde using sodium hydroxide as catalyst in ethanol
at room temperature. The chalcones were obtained in high yields (>80%).
General Procedure for the Synthesis of 3a–j
To a solution of thiophenol (1.2 mmol) and chalcone (1 mmol) in dichloromethane (15
mL), iodine (10 mol%) solution in dichloromethane (1 mL) was added and the mixture was
stirred at room temperature for 3 h. Then, the iodine was removed with diluted Na2S2O3
(0.06 M) and washed with CH2Cl2. The organic layer was dried over Na2SO4 and the
solvent removed under reduced pressure. The crude product was purified on a silica gel
column eluting with CHCl3/n-hexane (4:6) and/or crystallized in CHCl3/n-hexane (1:4).
According to our literature survey, synthesized compounds (except 3d,40 3e,41 and 3g42)
are unknown in literature. Spectral data and selected NMR spectra for 3a,j (Figures S1–S4)
are presented in the Supplemental Materials.
Spectral Data
1-(2-methoxyphenyl)-3-phenyl-3-(phenylthio)propan-1-one (3a). Yield 88%;
◦
◦
1
white crystal; mp 86 C–88 C. H NMR (400 MHz, CDCl3, ppm): δ = 7.55 (dd, J =
7.6, 1.2 Hz, 1H), 7.47–7.42 (m, 1H), 7.33–7.29 (m, 4H), 7.27–7.17 (m, 6H), 6.98–6.93
(m, 2H), 4.89 (dd, J = 7.6, 6.6 Hz, 1H), 3.86 (s, 3H), 3.72 (dd, J = 17.2, 8.2 Hz, 1H,
A part of AB system), 3.63 (dd, J = 17.2, 6.4 Hz, 1H, B part of AB system). 13C NMR
(100 MHz, CDCl3, ppm): δ = 199.4, 158.4, 141.5, 134.5, 133.6, 132.9 (2C), 130.5, 128.7
(2C), 128.3 (2C), 128.0 (2C), 127.9, 127.4, 127.2, 120.7, 111.4, 55.5, 49.8, 48.7. IR (KCl,
cm−1): 3056, 3027, 2969, 2937, 2832, 2360, 2341, 1671, 1656, 1596, 1577, 1482, 1454,
1288, 1240, 1164, 1022, 987, 759. Anal. Calcd. for C22H20O2S: C, 75.83; H, 5.79; S, 9.20.
Found: C, 75.69; H, 5.62; S, 9.08.
1-phenyl-3-(phenylthio)-3-o-tolylpropan-1-one (3b). Yield 88%; white crystal; mp
85 C–87 C. H NMR (400 MHz, CDCl3, ppm): δ = 7.91 (d, J = 7.6 Hz, 2H), 7.57 (t,
◦
◦
1

˙
I. KARAMAN ET AL.
584
J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.40–7.37 (m, 2H), 7.35–7.33 (m, 1H), 7.28 (t,
J = 3.0 Hz, 3H), 7.15 (t, J = 2.4 Hz, 3H), 5.22 (dd, J = 8.4, 5.6 Hz, 1H), 3.80 (dd, J =
17.4, 8.6 Hz, 1H, A part of AB system), 3.62 (dd, J = 17.4, 5.8 H z, 1H, B part of AB
system), 2.48 (s, 3H). 13C NMR (100 MHz, CDCl3, ppm): δ = 197.4, 138.9, 136.7, 136.4,
134.2, 133.3 (3C), 130.6, 128.9 (2C), 128.6 (2C), 128.1 (2C), 127.8, 127.2, 126.5, 126.2,
44.3, 43.9, 19.5. IR (KCl, cm−1): 3064, 3016, 2983, 2958, 2902, 2819, 2360, 2343, 1677,
1579, 1477, 1448, 1322, 1228, 1085, 981, 761, 740, 682. Anal. Calcd. for C22H20OS: C,
79.48; H, 6.06; S, 9.64. Found: C, 79.14; H, 6.05; S, 9.43.
1-phenyl-3-(phenylthio)-3-m-tolylpropan-1-one (3c). Yield 82%; yellow crystal;
mp 54 ◦C–56 ◦C. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.94 (d, J = 7.6 Hz, 2H), 7.57
(t, J = 7.0 Hz, 1H), 7.47–7.41 (m, 4H), 7.30–7.21 (m, 6H), 7.07 (br, d, J = 6.4 Hz, 1H),
5.42 (dd, J = 8.0, 6.0 Hz, 1H), 3.74 (dd, J = 17.2, 8.0 Hz, 1H, A part of AB system),
3.64 (dd, J = 17.2, 6.0 Hz, 1H, B part of AB system), 2.35 (s, 3H). 13C NMR (100 MHz,
CDCl3, ppm): δ = 197.1, 141.1, 138.1, 136.8, 134.6, 133.3, 132.7 (2C), 129.0 (2C), 128.7
(2C), 128.6, 128.5, 128.3, 128.2 (2C), 127.5, 124.9, 48.2, 44.8, 21.5. IR (KCl, cm−1): 3056,
2996, 2902, 2360, 2341, 1679, 1558, 1540, 1475, 1417, 1326, 1220, 1085, 979, 738, 684.
Anal. Calcd. for C22H20OS: C, 79.48; H, 6.06; S, 9.64. Found: C, 79.34; H, 5.92; S, 9.51.
1-(2-nitrophenyl)-3-phenyl-3-(phenylthio)propan-1-one (3f). Yield 74%; brown
◦
◦
1
crystal; mp 57 C–59 C. H NMR (400 MHz, CDCl3, ppm): δ = 8.07 (d, J = 8.0 Hz,
1H), 7.62–7.52 (m, 2H), 7.33–7.24 (m, 10H), 7.04 (dd, J = 6.8, 1.2 Hz, 1H), 4.84 (t, J =
7.2 Hz, 1H), 3.54–3.43 (m, 2H). 13C NMR (100 MHz, CDCl3, ppm): δ = 199.7, 145.4,
140.5, 137.7, 134.2, 133.8, 132.8 (2C), 130.6, 128.9 (2C), 128.6 (2C), 127.8 (2C), 127.7,
127.6, 127.5, 124.3, 48.8, 48.5. IR (KCl, cm−1): 3100, 3068, 3025, 3004, 2856, 2360,
2341, 1695, 1565, 1521, 1438, 1342, 1230, 1025, 860, 763, 746, 700, 613. Anal. Calcd.
for C21H17NO3S: C, 69.40; H, 4.71; N, 3.85; S, 8.82. Found: C, 69.29; H, 4.61; N, 3.73; S,
8.71.
3-(2-chlorophenyl)-1-(furan-2-yl)-3-(phenylthio)propan-1-one (3 h). Yield 82%;
yellow crystal; mp 77 ◦C–79 ◦C. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.49 (s, 1H), 7.42
(d, J = 7.6 Hz, 1H), 7.36–7.33 (m, 3H), 7.23–7.12 (m, 6H), 6.48 (br, s, 1H), 5.45 (t, J = 7.4
Hz, 1H), 3.52 (dd, J = 16.4, 7.0 Hz, 1H, A part of AB system), 3.47 (dd, J = 16.4, 7.6 Hz,
1H, B part of AB system). 13C NMR (100 MHz, CDCl3, ppm): δ = 185.5, 152.5, 146.6,
138.3, 133.7, 133.6, 133.1 (2C), 129.8, 128.9 (2C), 128.7, 128.6, 127.9, 127.0, 117.5, 112.5,
44.5, 43.8. IR (KCl, cm−1): 3120, 3085, 3060, 3021, 2931, 2360, 2341, 1671, 1565, 1465,
1328, 1245, 1079, 1035, 1016, 898, 765, 744, 682, 595. Anal. Calcd. for C19H15ClO2S: C,
66.56; H, 4.41; S, 9.35. Found: C, 66.47; H, 4.29; S, 9.28.
1-(4-methoxyphenyl)-3-(phenylthio)-3-(thiophen-2-yl)propan-1-one (3i). Yield
91%; white crystal; mp 72 ◦C–74 ◦C. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.92 (d, J =
8.6 Hz, 2H, AAꢁ part of AAꢁXXꢁ system), 7.41–7.38 (m, 2H), 7.31–7.26 (m, 3H), 7.15 (d,
J = 5.2 Hz, 1H), 6.93 (d, J = 8.6 Hz, 2H, XXꢁ part of AAꢁXXꢁ system), 6.86 (s, 1H), 6.83
(t, J = 4.2 Hz, 1H), 5.29 (t, J = 7.0 Hz, 1H), 3.86 (s, 3H), 3.65 (dd, J = 17.2, 7.8 Hz, 1H,
A part of AB system), 3.56 (dd, J = 17.2, 6.0 Hz, 1H, B part of AB system). 13C NMR
(100 MHz, CDCl3, ppm): δ = 195.0, 163.7, 145.6, 134.0, 133.0 (2C), 130.5 (2C), 129.7,
128.9 (2C), 127.8, 126.5, 125.5, 124.6, 113.8 (2C), 55.5, 45.3, 43.8. IR (KCl, cm−1): 3099,
3068, 2969, 2933, 2890, 2838, 2360, 2341, 1671, 1600, 1571, 1508, 1419, 1349, 1265,
1226, 1172, 1022, 981, 829, 748, 690. Anal. Calcd. for C20H18O2S2: C, 67.76; H, 5.12; S,
18.09. Found: C, 67.64; H, 5.01; S, 17.94.
1-(2-hydroxyphenyl)-3◦-(phenylthio)-3-(thiophen-2-yl)propan-1-one (3j). Yield
◦
1
89%; yellow crystal; mp 77 C–79 C. H NMR (400 MHz, CDCl3, ppm): δ = 12.12

SYNTHESIS AND SCREENING ANTIMICROBIAL ACTIVITIES
585
(s, 1H, –OH), 7.71 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.4 Hz, 1H), 7.42–7.40 (m, 2H),
7.31–7.29 (m, 3H), 7.19 (d, J = 4.4 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.93–6.86 (m,
3H), 5.26 (t, J = 6.8 Hz, 1H), 3.73 (dd, J = 17.2, 8.0 Hz, 1H, A part of AB system), 3.66
(dd, J = 17.2, 6.2 Hz, 1H, B part of AB system). 13C NMR (100 MHz, CDCl3, ppm):
δ = 202.4, 162.6, 145.0, 136.8, 133.6, 133.2 (2C), 129.8, 129.0 (2C), 128.1, 126.6, 125.6,
124.8, 119.3, 119.1, 118.7, 45.2, 43.6. IR (KCl, cm−1): 3120, 3075, 3048, 2948, 2888,
2842, 2360, 2341, 1641, 1577, 1475, 1436, 1342, 1278, 1207, 1157, 1035, 983, 927, 846,
755, 730, 632. Anal. Calcd. for C19H16O2S2: C, 67.03; H, 4.74; S, 18.84. Found: C, 66.91;
H, 4.63; S, 18.73.
Antimicrobial Activity
The antibacterial activities of 1,3-diaryl-3-(phenylthio)propan-1-one derivatives 3a–j
against 10 microorganisms, i.e., two yeasts (Candida albicans ATCC 1213 and Candida
utilis KUEN 1031), four Gram-positive bacteria (Bacillus cereus DSM 4312, Bacillus sub-
tilis ATCC 6633, Staphylococcus aureus ATCC 29213, and Streptococcus pyogenes ATCC
176), and four Gram-negative bacteria (Proteus vulgaris KUEN 1329, Escherichia coli
111, Pseudomonas aeruginosa ATCC 9027, and Salmonella enteridis ATCC 13076), were
determined with the disc diffusion method43,44 using 100 mL of suspension containing 108
CFU/mL of bacteria and 106 CFU/mL of yeasts spread on nutrient agar (NA), Sabouraud
dextrose agar (SDA), and potato dextrose agar (PDA) medium. The minimum inhibitory
concentration (MIC) values for compounds (3a, 3f, 3h, 3i, 3j) defined as the lowest con-
centration of the compound preventing the visible growth were determined by using the
micro dilution method.45,46
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