One pot three components microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one as antimicrobial agents

Article abstract of DOI:10.1016/j.bmcl.2014.05.051

A one-pot, three-component, microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one (4a-n) was carried out by using N,N-dimethylformamide as a solvent with high product yield. Among these synthesized compounds (4f, 4g, 4l and 4m) were found to be a broad spectrum molecule active against all bacterial and fungus strains tested, except fungus Aspergillus niger. Amongst the compounds (4g, 4l and 4m) were found to be more potent than respective standard drugs used in the experiment against Candida albicans, Staphylococcus aureus and Aspergillus flavus, respectively. All synthesized compounds were also tested for their cytotoxic activity against HeLa and MCF-7 cell lines by the sulforhodamine B (SRB) assay. This study shows that all compounds were non-cytotoxic in nature, and confirmed their antimicrobial specificity apart from any general cytotoxicity.

Full text of DOI:10.1016/j.bmcl.2014.05.051

Accepted Manuscript
One pot three components microwave assisted and conventional synthesis of
new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one as antimi-
crobial agents
Dattatraya N. Pansare, Nayeem A. Mulla, Chandrakant D. Pawar, Vikas R.
Shende, Devanand B. Shinde
PII:
S0960-894X(14)00551-4
DOI:
http://dx.doi.org/10.1016/j.bmcl.2014.05.051
BMCL 21665
Reference:
Bioorganic & Medicinal Chemistry Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
6 January 2014
5 May 2014
15 May 2014
Please cite this article as: Pansare, D.N., Mulla, N.A., Pawar, C.D., Shende, V.R., Shinde, D.B., One pot three
components microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted)
thiazolidin-4-one as antimicrobial agents, Bioorganic & Medicinal Chemistry Letters (2014), doi: http://dx.doi.org/
10.1016/j.bmcl.2014.05.051
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One pot three components microwave assisted and conventional synthesis
of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one as
antimicrobial agents
Dattatraya N. Pansare,a Nayeem A. Mulla,b Chandrakant D. Pawar ,a Vikas R. Shende,b
Devanand B. Shinde *a
aDepartment of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad 431 004, MS, India.
bDepartment of Biochemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad 431 004, MS, India.
Tel No.: +91 0240-2403308 Fax No.: +91 0240-2400413
*Corresponding author E-mail: dbsdattatraya10@rediffmail.com
Abstract
A one-pot, three-component, microwave assisted and conventional synthesis of new
3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one (4a-n) was carried out by
using N, N-dimethylformamide as a solvent with high product yield. Among these
synthesized compounds (4f, 4g, 4l and 4m) were found to be a broad spectrum molecule
active against all bacterial and fungus strains tested, except fungus A. niger. Amongst the
compounds (4g, 4l and 4m) were found to be more potent than respective standard drugs used
in the experiment against C. albicans, S. aureus and A. flavus respectively. All synthesized
compounds were also tested for their cytotoxic activity against HeLa and MCF-7 cell lines by
the sulforhodamine B (SRB) assay. This study shows that all compounds were non-cytotoxic
in nature, and confirmed their antimicrobial specificity apart from any general cytotoxicity.
Keywords: Thiazolidin-4-one, microwave-assisted synthesis, 2-amino-5-chlorophenol,
antimicrobial, cytotoxicity.
The structural and therapeutic diversity coupled with the commercial viability of
different types of small molecules has fascinated organic and medicinal chemists. There has
been considerable most of interest in the chemistry of thiazolidin-4-one moiety. The
derivatives of 4-thiazolidinone nucleus have also occupied a unique place in the field of
medicinal chemistry.1 The thiazolidin-4-one moiety display a wide range of biological
activities like antibacterial,2 anti-inflammatory,3,4 anticancer,5-8 anti-tuberculosis,9
anticonvulsant10 and analgesic11 activities. Earlier studies on the pharmacological activities of
thiazolidin-4-ones showed wide spectrums of antimicrobial activities.12-14 Microwave assisted
1

reactions have become an established tool for the high-speed synthesis of novel chemical
entities.15 Many chemical reactions are accelerated rate of reaction because of selective
absorption of MW energy. The application of microwave irradiation is the use of catalysts or
mineral supported reagents, under solvent-free conditions, enables organic reactions to occur
expeditiously at ambient pressure, thus providing unique chemical processes with special
attributes such as enhanced reaction rates and higher yields.16,17 The thiazolidin-4-ones
derivatives has been known for over 50 years, so there have been several attempts to design
antimicrobial agents based on this heterocycle. In continuation of our work,18 on the synthesis
of bioactive compounds, we have synthesized some thiazolidin-4-ones analogues. For the
development of new heterocyclic compounds and antimicrobial screening, we have
discovered an efficient method for the synthesized of thiazolidin-4-ones analogues. There are
various reports available on thiazolidin-4-ones derivatives as antimicrobial agents.19-22 With
this in mind, we initiated a program to synthesized thiazolidin-4-ones derivatives as
antimicrobial agent by preparing hybrid molecules having the similar features of reported
potent antimicrobial agents (Figure 1).
To synthesize a series of new thiazolidin-4-ones, which have different
pharmacologically active groups, these are exhibited antimicrobial activities. We have
successfully synthesized series of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted)
thiazolidin-4-one (4a-n) (Scheme 1) by using one-pot, three-component system, under
microwave assisted technique as well as a conventional method using N, N-
dimethylformamide (DMF) as a solvent with 2-3 drops of glacial acetic acid in catalytic
amounts. The synthesized compounds are tested for their in vitro antimicrobial activities
against fungal and bacterial strains as well as for cytotoxicity against cultured mammalian
cells. The synthesized compounds were characterized on the basis of IR, 1H NMR, 13C NMR,
Elemental analysis and mass spectral data.
Our current investigation describes the convenient synthesis of 3-(4-chloro-2-
hydroxyphenyl)-2-(substituted)thiazolidin-4-one using DMF as a solvent under microwave
assisted as well as conventional synthesis with high yield in a short time period. This method
is unique, rapid and convenient for the synthesis of new thiazolidin-4-one compounds. We
herein report the synthesis and screening of antimicrobial activity and cytotoxicity of a series
of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one. The syntheses of new
3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one were achieved following the
step outlined (Scheme 1). Microwave used in the study was MicroSYNTH Lab station of
2

Ethusi Milestone with temperature control (Scheme 1, Method A). A one-pot, three-
component, microwave assisted as well as conventional synthesis by using 2-amino-5-
chlorophenol with substituted aldehydes and 3-4 drops of glacial acetic acid with DMF as a
solvent and thioglycolic acid reacted with them to give the compounds (4a-n) (Table 1). The
possible mechanism of the reaction is shown in Scheme 2. The initial reaction of 2-amino-5-
chlorophenol with benzaldehyde produces imine, which at the reflux temperature is
dehydrated or loss of water. When the mercaptoacetic acid reacts with imine, thiazolidinones
product is formed by loss of water. All of the compounds were obtained in good yield with a
short reaction time period in microwave assisted synthesis. These compounds were
characterized on the basis of spectral analysis. The IR spectrum of representative compound
3-(4-chloro-2-hydroxyphenyl)-2-phenylthiazolidin-4-one (4a), IR absorption bands in the
wavenumber show 3380 cm-1 that is due to a hydroxyl group, 1683 cm-1 that is due to a
carbonyl group. The mass spectrum revealed a molecular ion peak at m/z was 306 (M+1)
1
corresponding to a molecular formula C15H12ClNO2S. The H NMR spectrum of the
compound (4a) has been shown doublet of methylene proton in the range of δ 4.46–4.57 (d,
1H, CH2), 4.60–4.69 (d, 1H, CH2), 5.72 (s, 1H, OH), 6.20 (s, 1H, S–CH–N), 7.01–7.20 (m,
3H, Ar-H), 7.23–7.38 (m, 5H, Ar-H).
All the synthesized compounds (4a-n) were screened for their in vitro antimicrobial
activity against two gram positive bacteria; Bacillus subtilis (NCIM-2063)
and
Staphylococcus aureus (NCIM-2901), two gram negative bacteria; Escherichia coli (NCIM-
2256), Salmonella typhimurium (NCIM-3471) and four fungal strains; Candida albicans
(NCIM-3471), Aspergillus flavus (NCIM-539) Aspergillus niger (NCIM-1196) and
Cryptococcus neoformans (NCIM- 3378). In order to investigate the antimicrobial properties
of the compounds, Minimum Inhibitory Concentration (MIC), Minimum Bactericidal
Concentration (MBC) and Minimum Fungicidal Concentration (MFC) were found out by
modified macrodilution technique.23-27 For the Bacterial strains MIC determinations were
performed by a serial macrodilution technique using 96-well microtiter plate reader.
Investigated compounds were prepared in saline (0.8% NaCl) solution, containing 5%
Dimethyl sulfoxide (DMSO) for dissolution of compounds. All microbial strains were
incubated with different concentration of each compound in 96-well microtiter plate for 20 h
at 37 ºC on Rotary shaker (160 rpm). After incubation the lowest concentration value without
growth were defined as MICs. For the Fungal strains agar dilution technique, on Potato
Dextrose Agar (PDA) Medium, were used for MIC determination. The MBC and MFC of
3

compounds were determined by serial sub cultivation after inoculated for 72 h with tested
compounds dissolved in saline containing 5% DMSO. The lowest concentration with no
visible growth was defined as MBC/MFC indicating 99.5% killing of the original inoculums.
All the experiments performed in triplicates and mean reading is taken as a final reading. 5%
DMSO was used as a negative control along with Ciprofloxacin and Ampicillin as the
standard antibacterial drug and Fluconazole and Miconazole as the standard antifungal drug
(Table 2).
All the synthesized compounds were also tested for their general cytotoxicity on two
mammalian cell lines HeLa and MCF-7, human cervical and human breast cancer cell line
respectively (Table 3). These cytotoxic studies of the compounds are performed to test their
general cytotoxicity, if any, due to their nonspecific binding to the basic cell macromolecules
like proteins, plasma membrane, carbohydrates etc., and also to check their biocompatibility
to the eukaryotic cells. These tests are not performing to test their anticancer activity. The
cytotoxicity test is performed as previously mentioned SRB colorimetric assay.28
Cytotoxicity of the compounds was determined by calculating their IC50 values,
concentration of compound required to inhibit 50% of cell growth compared to untreated
control cells. IC50 values were presented in micro molar (µM) concentration. Adriamycin
(Doxorubicin) was used as positive control for the comparison of cytotoxicity of synthesized
compounds. Assays were performed in triplicate on three independent experiments and their
mean values are taken as a final reading. Thiazolidin-4-one based compounds were
synthesized by microwave irradiation as well as conventional heating with DMF and glacial
acetic acid.29
From the antimicrobial activity data (Table 2), it is clearly observed that many of the
synthesized compounds were shows prominent antimicrobial activity. Some compounds were
narrow spectrum active against only one fungal or bacterial strain while some of them were
found to be a broad spectrum active against both fungal and bacterial strains. Amongst series
the compounds (4f, 4g, 4l and 4m) were found to broad spectrum molecule, they were active
against all tested bacteria strains and fungus A. flavus and C. albicans. They were also most
active molecules among the series with (4g) and (4m) were more potent than standard
antifungal drugs Fluconazole and Miconazole, against C. albicans and A. flavus respectively,
having MIC value 3.0 µg/mL each. The compound (4l) was more potent than standard drugs
Ciprofloxacin and Ampicillin against S. aureus with MIC 6.0 µg/mL. The MIC value of this
group of molecules for remaining bacterial and fungal strains are in the range of 15 to 35
4

µg/mL, except for A. niger. The fungal strain, A. niger shows higher level of resistance to
nearly all synthesized compounds and in most of the cases this resistance was reported up to
MIC of 100 µg/mL. In the series, on the other hand, some narrow spectrum molecules,
including compounds (4a, 4d, 4e, 4h, 4j and 4n) were also obtained which are active against
selective strains. Among them (4a) was specifically active towards S. aureus (MIC 25
µg/mL), (4d) was active towards against Gram positive bacteria (MIC 20 to 25 µg/mL). The
compound (4e) active against Gram positive bacteria (MIC 20 to 35 µg/mL) and A. flavus
(MIC 35 µg/mL). The compounds (4h) and (4n) active against S. aureus (MIC 25 and 35
µg/mL respectively). The compound (4j) has been active against A. flavus (MIC 25 µg/mL)
with B. subtilis (MIC 35 µg/mL). The remaining compounds (4b, 4c, 4i and 4k) were having
very high MIC values and therefore these are considered as inactive compounds as per as
antimicrobial activity concerned.
The structure activity relationship of the series can be explained as,
The results of the antimicrobial screening demonstrated some definite and interesting
facts about the structure activity relationship (SAR) of synthesized molecules. In the majority
of cases, the dependence of the activity profile on structural modifications of the molecule is
clear and fascinating. Strain specificity and variation in the activity profile of molecules are
also directly attributed to the structural variations in molecules. The important highlights of
structure-activity relationship are.
•
•
•
Effect of the substituent on phenyl ring: The presence of phenyl ring (4a) at C2
position of the thiazolidinone nucleus, without any substitution at para and ortho
position, which makes the molecule specifically active towards bacterium S. aureus.
Effect of nitro group: The electron withdrawing nitro group substitution on the phenyl
ring at the para position (4b) make the molecule inactivate. This may due to its
electron withdrawing effect on phenyl ring.
Effect of chloro group: The chloro group has a crucial role in determined the activity
of molecules. This group affects the activity of molecules by its number as well as its
position to phenyl ring. Substitution of the chloro group at para positions on the
phenyl ring (4d) make the molecule specifically active towards Gram positive
bacteria B. subtilis and S. aureus. On the other hand, substitution of chloro group at
ortho positions (4e) makes the molecule active against Gram positive bacteria as well
as against A. flavus. This clearly indicates that the change in position of the chloro
group from para to ortho on the phenyl ring preserve its effects against Gram positive
5

bacteria and a make molecule additionally active against A. flavus. These changes of
para to ortho are favorable regarding the development of broad spectrum molecule
active against bacteria and fungi. However the substitution of two chloro group at
ortho and para position (4c) gives the inactive molecule, not even active against
Gram positive bacteria. This may be due to the larger size of molecules or increase in
total electronegative effect on the phenyl ring caused by the addition of the extra
chloro group, in either way hampering the binding of molecules to its target site and
make it inactive in nature.
•
Effect of methoxy group: The substitution of electron donating methoxy group at
ortho (4f) and ortho, para position (4g) on the phenyl ring gives the broad spectrum
properties of molecules, which is active against all bacterial and fungal strains tested,
except A. niger. These observations clearly show that, for the development broad
spectrum antimicrobial molecule, electron donating group is better than electron
withdrawing group (the nitro group which make molecule inactive and chloro group
make molecule active against Gram positive bacteria and A. flavus) on phenyl ring.
Further, the MIC data shows that (4g) is more potent than (4f), indicates that the
addition of the extra methoxy group at the para position somehow increases the
activity of molecules.
•
Effect of fluoro group: Substitution of fluoro group at para positions (4h) make the
molecule narrow spectrum, active only against S. aureus, while substitution at the
meta position (4i) make the molecule inactive. This variation in activity may be
attributed to the change in position of fluoro group, from para to meta on the phenyl
ring.
•
Effect of heterocyclic ring: The presence of thiophenyl moiety instead of phenyl ring
at C2 position on the thiazolidinone nucleus (4j) give the molecule specificity against
B. subtilis and A. flavus. However, substitution of pyridinyl moiety instead of phenyl
rings at C2 position of the thiazolidinone nucleus (4k) resulted in the formation of
inactive molecule and therefore this heterocyclic ring is not suitable to develop
antimicrobial compounds. On the other hand the substitution of 4-methylthiazole
moiety (4m) make the molecule broad spectrum, and its activity is intermediate
between the (4l) and (4f) i.e. lower than (4l) but higher than (4f).
•
Effect of hydroxyl group: Substitution of the electron donating hydroxyl group
attached to the phenyl ring at the para position (4l) gives the most potent and broad
6

spectrum molecule of the series. The compound (4l) is more active than (4f) and (4g),
indicates that the hydroxyl group at para position is a better option than the methoxy
group at ortho (4f) or ortho and para (4g) position, as per as antimicrobial potential
molecules.
•
Effect of nitrile groups: The electron withdrawing nitrile group substitution on the
phenyl ring at the para position (4n) render the molecule narrow spectrum, active
only against S. aureus.
The compounds were synthesized by both conventional as well as microwave
irradiation techniques with reduced reaction time and increase the yield of product. The
synthesized compounds (4f, 4g, 4l and 4m) are found to be broad spectrum molecule; they
are active against all tested bacteria strains and fungus A. flavus and C. albicans. Important
finding is that the compounds (4g) and (4m) more potent than standard antifungal drugs. The
compound (4l) was more potent than standard drugs Ciprofloxacin and Ampicillin against S.
aureus. SAR observations confirm that, electron donating group, such as methoxy, is suitable
over electron withdrawing group, including nitro and chloro groups, on the phenyl ring for
the development of broad spectrum antimicrobial compounds. For all active molecules,
values for MBC and MFC are higher than the corresponding MIC value in all cases. This
may be due to the ‘static’ and not the cidal, mode of action of molecules on all strains. Thus
the outstanding antimicrobial properties of this new class of substances are diverse and vary
considerably with antimicrobial strains, hence required further detailed investigation in order
to clarify the mode of action of each molecule at the molecular level.
Acknowledgement
The authors are thankful to Indian Council of Medical Research, New Delhi, for the
financial assistance under the major research projects IRIS Cell No. 2008-06260, also
thankful to the Head, Department of Chemical Technology, Dr. Babasaheb Ambedkar
Marathwada University, Aurangabad 431004 (MS), India for providing the laboratory
facility.
7

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29. Experimental section: 2-amino-5-chlorophenol, substituted aldehydes, thioglycolic acid,
DMF, glacial acetic acid and various solvents were commercially available. The major
chemicals were purchased from Sigma Aldrich and Avra labs. Reaction progress was
monitored by TLC on silica gel precoated F254 Merck plates. Developed plates were
examined with ultraviolet lamps (254 nm). IR spectra were recorded on a FT-IR
(Bruker). Melting points were recorded on SRS Optimelt, melting point apparatus and
1
are uncorrected. H NMR spectra were recorded on a 400 MHz Bruker spectrometer
and 13C NMR spectra were recorded on a 100 MHz Bruker spectrometer are reported as
parts per million (ppm) downfield from a tetramethylsilane internal standard. The
following abbreviations are used, singlet (s), doublet (d), triplet (t), quartet (q),
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9

Table 1
Synthesis of 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one (4a-n)a.
Yield b (%)
Time
Sr.
Aldehydes
Melting
No.
point (ºC)
MWc
Con.d
(h)
MWc
98
Con.d
90
(min)
9
Benzaldehyde
3
89-91
4a
4-nitrobenzaldehyde
2,4-dichlorobenzaldehyde
4-chlorobenzaldehyde
2-chlorobenzaldehyde
4-methoxybenzaldehyde
2,4-dimethoxybenzaldehyde
4-fluorobenzaldehyde
3-fluorobenzaldehyde
thiophene-2-carbaldehyde
2-Pyridinecarbaldehyde
4-hydroxybenzaldehyde
4-methylthiazole-5-
9
10
9
3
3
2
3
2
2
2
3
3
3
3
3
98
97
96
98
97
97
98
98
96
97
98
96
92
92
90
90
91
92
90
92
90
91
90
90
192-194
133-135
119-121
126-128
45-46
4b
4c
4d
4e
4f
10
8
8
48-49
4g
4h
4i
9
127-129
139-141
84-86
9
8
4j
8
102-104
40-42
4k
4l
9
10
44-46
4m
carbaldehyde
4-formylbenzonitrile
9
3
96
92
140-142
4n
aReaction condition (4a-n)
Method A: Microwave-assisted synthesis: Glacial acetic acid, N, N-dimethylformamide, 110 ºC, 8-10 min.
Method B: Conventional synthesis: Glacial acetic acid, N, N-dimethylformamide, reflux 2-3 h.
bIsolated yields.
cMicrowave
dConventional
10

Table 2
Antimicrobial activity of the synthesized compounds (4a-n).
Compound
MIC, MBC and MFC Values (µg/mL)a
B.s.
S.a.
E.c.
S. t.
C.a.
A.f.
A.n.
C. n.
4a
4b
4c
4d
MIC
MBC/MFC
MIC
60
85
25
40
65
55
120
80
60
115
95
80
115
75
90
120
100
160
70
70
125
90
125
90
100
140
80
85
MBC/MFC
MIC
140
90
155
70
135
75
155
90
135
85
135
100
150
95
MBC/MFC
MIC
160
25
160
20
150
50
155
65
160
70
140
90
145
65
MBC/MFC
45
45
165
155
160
155
165
160
4e
4f
MIC
MBC/MFC
20
40
35
55
80
140
65
135
55
140
35
50
100
155
90
135
MIC
30
30
35
25
15
15
80
65
MBC/MFC
MIC
40
30
45
40
15
25
45
30
50
110
35
20
3.0
20
10
15
150
65
155
70
4g
4h
4i
MBC/MFC
45
17.5
120
120
MIC
MBC/MFC
55
150
25
45
70
145
60
140
65
150
90
140
50
140
90
145
MIC
MBC/MFC
100
155
80
160
70
145
90
155
95
165
90
140
100
165
85
140
4j
MIC
35
55
60
150
60
85
160
90
70
155
85
100
160
55
25
45
70
155
80
95
160
75
MBC/MFC
MIC
4k
85
100
165
MBC/MFC
165
155
165
150
155
155
150
4l
MIC
15
6.0
20
25
25
20
55
60
MBC/MFC
MIC
25
30
20
15
35
15
45
20
40
30
35
115
80
115
55
4m
4n
3.0
MBC/MFC
MIC
55
100
20
35
20
90
40
55
45
90
20
60
135
100
95
85
MBC/MFC
MIC
140
6.25
13.0
145
120
115
7.5
8.0
140
115
145
125
Ciprofloxacin
6.25
7.5
-
-
-
-
-
-
-
-
MBC
13.0
8.0
Ampicillin
Fluconazole
Miconazole
MIC
MBC
MIC
MFC
MIC
MFC
12.5
17.5
12.5
17.5
-
-
-
-
12.5
17.5
-
-
-
-
12.5
17.5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
10.0
22.5
3.25
12.5
6.25
16.5
3.25
12.5
6.25
16.5
3.25
12.5
6.25
16.5
3.25
12.5
aAll values are the average of three readings and expressed in µg/mL.
B.s.- Bacillus subtilis (NCIM-2063); S.a.- Staphylococcus aureus (NCIM-2901); E.c.- Escherichia coli (NCIM-
2256); S. t.- Salmonella typhimurium (NCIM-3471);C.a.- Candida albicans (NCIM-3471); A.f.- Aspergillus
flavus (NCIM-539); A.n.- Aspergillus niger (NCIM-1196); C. n.- Cryptococcus neoformans (NCIM- 3378).
(-) denotes not tested.
11

Table 3
Cytotoxic activity of the synthesized compounds (4a-n).
Sr. No. Compounds
(IC50)a µM b
Sr. No. Compounds
(IC50)a µM b
HeLa c MCF-7 d
HeLa c MCF-7 d
1
2
3
4
5
6
7
63.7
52.2
49.5
64.4
62.8
51.6
68.2
<0.1
56.8
41.0
48.4
56.2
56.2
48.6
68.5
<0.1
72.4
67.3
66.6
87.2
63.8
78.5
83.2
68.7
65.8
64.9
88.7
59.4
75.7
81.2
4a
8
4h
4i
4b
9
4c
10
11
12
13
14
4j
4d
4k
4l
4e
4f
4g
4m
4n
Adriamycine
aIC50 concentration of drug that decreases the viability of the cells by 50% compared to non-treated control
cells.
bValues are the average of three readings.
cHeLa: Human cervical cancer cell line.
dMCF-7: Human Breast cancer cell line.
eAdriamycin : Positive control compound.
12

Cl
Cl
N
O
S
S
N
N
N
O
S
S
O
Compound A
Compound B
MIC =12.5 µg/mL
MIC = 6.25 µg/mL
Cl
Ar
S
N
OH
O
4 (a-n)
Fig. 1. Previously reported antimicrobial agents and synthesized compounds.
13

Scheme 1. Synthesis of 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one (4a-
n).
Method A: Microwave-assisted synthesis: Glacial acetic acid, DMF, 110 ºC, 8-10 min.
Method B: Conventional synthesis: Glacial acetic acid, DMF, reflux 2-3 h.
Scheme 2. Plausible reaction mechanism for the synthesis of thiazolidin-4-one
HO
O
HO
OH
Ar
H
H2N
Cl
+
Ar
N
H
Cl
-H2O
HO
Ar
Cl
Ar
N
Cl
N
S
-H2O
O
Imine
OH
HS
O
OH
Product
14

One pot three components microwave assisted and conventional synthesis
of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one as
antimicrobial agents
Dattatraya N. Pansare,a Nayeem A. Mulla,b Chandrakant D. Pawar ,a Vikas R. Shende,b
Devanand B. Shinde a*
aDepartment of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad 431 004, MS, India.
bDepartment of Biochemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad 431 004, MS, India.
Tel No.: +91 0240-2403308 Fax No.: +91 0240-2400413
*Corresponding author E-mail: dbsdattatraya10@rediffmail.com
Graphical abstract
Compounds (4a-n) were synthesized and their MIC data shows that majority of the
synthesized compounds exhibited good antimicrobial activity in-vitro.
15