Synthesis, characterization, anticancer, and antioxidant activity of some new thiazolidin-4-ones in MCF-7 cells

Article abstract of DOI:10.1007/s00044-012-0071-5

There are limited studies centring on the potential of thiazolidin-4-ones as anticancer agents. In this study, a new series of 2-(3-substituted-1H- pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1, 3-thiazolidin-4-one (4a-o) have been synthesized by cyclo-condensation reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4- triazole-3-thione (3a-o) and thioglycolic acid. The structures of all the synthesized compounds were confirmed by elemental analysis, spectral techniques like IR, ¹H NMR, and mass spectroscopy. Few compounds exhibited dose-dependent cytotoxic effect in MTT assay in human breast cancer (MCF-7) cells. Apoptotic degradation of DNA due to action of potent thiazolidin-4-ones was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). A concentration-dependent increase in tail length and olive tail moment was observed when treated with thiazolidin-4-ones. In vitro antioxidant studies like DPPH and ABTS-free radical scavenging assays-indicated moderate activity of thiazolidin-4-ones.

Full text of DOI:10.1007/s00044-012-0071-5

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-012-0071-5
ORIGINAL RESEARCH
Synthesis, characterization, anticancer, and antioxidant activity
of some new thiazolidin-4-ones in MCF-7 cells
•
Arun M. Isloor Dhanya Sunil Prakash Shetty
•
•
•
Shridhar Malladi K. S. R. Pai Naseer Maliyakkl
•
Received: 17 December 2011 / Accepted: 19 April 2012
Ó Springer Science+Business Media, LLC 2012
Abstract There are limited studies centring on the
potential of thiazolidin-4-ones as anticancer agents. In this
study, a new series of 2-(3-substituted-1H-pyrazol-4-yl)-3-
(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-
4-one (4a–o) have been synthesized by cyclo-condensation
reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-
ylmethylidene)amino]-2H-1,2,4-triazole-3-thione (3a–o) and
thioglycolic acid. The structures of all the synthesized
compounds were confirmed by elemental analysis, spectral
A concentration-dependent increase in tail length and olive
tail moment was observed when treated with thiazolidin-4-
ones. In vitro antioxidant studies like DPPH and ABTS-
free radical scavenging assays-indicated moderate activity
of thiazolidin-4-ones.
Keywords Thiazolidin-4-one ꢀ Cytotoxicity ꢀ
DNA fragmentation ꢀ Antioxidant activity
1
techniques like IR, H NMR, and mass spectroscopy. Few
compounds exhibited dose-dependent cytotoxic effect in
MTT assay in human breast cancer (MCF-7) cells. Apop-
totic degradation of DNA due to action of potent thiaz-
olidin-4-ones was analysed by agarose gel electrophoresis
and visualized by ethidium bromide staining (comet assay).
Introduction
Cancer, characterized by uncontrolled, rapid, and patho-
logical proliferation of abnormal cells, is the second lead-
ing cause of human death after cardiovascular diseases in
developing as well as advanced countries (Bandgar et al.,
2010). Although there are many therapeutic strategies
including chemotherapy and radiotherapy, high-systemic
toxicity, and drug resistance limit the successful outcomes
in most cases.
A. M. Isloor (&) ꢀ S. Malladi
Breast cancer is one of the oldest known forms of
tumors in humans. Globally, breast cancer is the most
common cancer in women, after skin cancer, representing
16 % of all female cancers (Porter, 2008). Since 1970s, the
number of cases has significantly increased worldwide,
partly attributed to this lifestyle. The treatment of breast
cancer starts with surgery, and then chemotherapy, radia-
tion, or they are given in combinations. One of the most
common treatments is cyclophosphamide plus doxorubicin;
these drugs damage DNA in the cancer, but also cause
serious side effects in normal cells (Lee et al., 2002).
Damage to the heart muscle is the most dangerous com-
plication of doxorubicin. Therefore novel diagnosis, treat-
ment, and prevention approaches are immediately required
for breast cancer therapy. The development of effective,
Medicinal Chemistry Laboratory, Department of Chemistry,
National Institute of Technology, Surathkal, Mangalore 575 025,
India
e-mail: isloor@yahoo.com
D. Sunil
Department of Chemistry, Manipal Institute of Technology,
Manipal University, Manipal 576 104, India
P. Shetty
Department of Printing and Media Engineering, Manipal
Institute of Technology, Manipal University, Manipal 576 104,
Karnataka, India
K. S. R. Pai ꢀ N. Maliyakkl
Department of Pharmacology, Manipal College of
Pharmaceutical Sciences, Manipal University,
Manipal 576 104, India
123

Med Chem Res
selective, and less toxic anticancer agents remains an
important and challenging goal in medicinal chemistry.
In recent years, numerous 1,2,4-triazole derivatives have
been found to be associated with antimicrobial (Isloor
et al., 2009; Demirbas et al., 2004; Malladi et al. 2011a, b;
Swamy et al., 2006; Palekar et al., 2009), anti-inflamma-
tory (Malladi et al. 2011a), analgesic (Mathew et al.,
2007), and anticancer (Holla et al., 2002, Ibrahim 2009,
Padmavathi et al., 2009) properties. AK-2123 (Sanazol), a
nitrotriazole hypoxic cell sensitizer has apparently
improved results in head and neck cancers, uterine cervical
cancers, and other solid tumors when added to radical
radiotherapy (Dobrowsky et al., 2005). Further, existing
literature indicates 1,2-pyrazole derivatives to possess
various biological activities (Chandrakantha et al., 2011;
Vijesh et al., 2010; Vijesh et al. 2011a, b). Non-steroidal
aromatase inhibitors obtained from triazole derivatives are
currently used in the treatment of breast cancer (Brueg-
gemeier et al., 2004). Thiazolidinones were reported to
exhibit several biological properties (Amir and Azam,
2004; Hafez and El-Gazzar, 2009; Siddiqui et al., 2007;
Selvi and Rajendran, 2007; Wilson et al., 2008).
substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4-
triazole-3-thiones (Schiff bases) (3a–o) (Sunil et al.,
2011). The new 2-(3-substituted-1H-pyrazol-4-yl)-3-(3-
substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-4-
ones (4a–o) were synthesized by the cyclo-condensation of
the Schiff bases with thioglycolic acid in dimethyl form-
amide in presence of anhydrous zinc chloride (Selvi and
Rajendran, 2007). The reaction sequence has been pre-
sented in Scheme 1 and the plausible mechanism for the
formation of thiazolidinone has been given in Scheme 2.
The structures of the newly synthesized compounds were
established by spectral data and elemental analysis. Thin
layer chromatography was conducted on 0.25 9 10-3
m
silica gel plates to monitor the progress and to check the
purity of the compounds. A 1:1 mixture of ethyl acetate and
petroleum ether solution was used as the eluent. Visualiza-
tion was made by using iodine vapors. The IR spectra in KBr
pellets were recorded using Schimadzu FTIR 8400S spec-
trophotometer. 1H NMR spectra were recorded in deuterated
dimethyl sulphoxide in AV500 NMR spectrometer using
tetramethyl silane as internal standard. The mass spectra
were recorded in a Schimadzu GCMS-QP5050 mass spec-
trometer. The elemental analysis was done in Flash thermo
1112 series CHN analyser. Melting points were determined
by open capillary method and were uncorrected.
Reactive oxygen species (ROS)-like superoxide anion,
hydroxyl radical, and hydrogen peroxide attack various
biological molecules like proteins, enzymes, DNA, and
other biomolecules. Oxidative stress conditions give rise to
a number of inflammatory, metabolic disorders, cellular
aging, and cancer (Bandgar et al., 2009, 2010). Antioxi-
dants inhibit oxidative damage induced by free radicals and
ROS. Thus, antioxidant therapy has also gained immense
significance in the treatment of cancer. In view of the wide
spectrum of medicinal applications of triazole, pyrazole,
and thiazolidinone derivatives and in continuation of our
research on new anticancer molecules, we hereby report the
synthesis, characterization, anticancer, and antioxidant
activities of some new thiazolidin-4-ones.
IR spectra of the newly synthesized thiazolidinones
displayed a strong absorption band due to C=O stretching
1
at 1,730 cm-1. The H NMR spectra showed a singlet at
5.05 ppm due to the methylene protons in thiazolidinone
ring. The singlet corresponding to the tertiary methine
protons of thiazolidinone ring was observed at 5.35 ppm.
The O-CH2 protons resonated at 5.63 ppm and were
observed as a singlet. The pyrazole C–H protons resonated
at 6.92 ppm. Singlet at 12.20 ppm is due to pyrazole NH,
the broad singlet at 13.78 ppm was due to the S–H protons.
The aromatic protons were seen resonating between 7.1
and 7.7 ppm. The mass spectra of all newly synthesized
thiazolidin-4-ones showed molecular ion peaks which were
in accordance with their respective molecular masses.
Results and discussion
Chemistry
Pharmacology
3-substituted-4-amino-5-mercapto-1,2,4-triazoles (1) were
synthesized through multistep reaction of substituted phe-
nols (Sunil et al., 2011). 3-substituted-1H-pyrazole car-
baldehydes (2) were prepared using semicarbazones by
Vilsmeier Haack reaction (Vijesh et al., 2011a, b) using
phosphorous oxychloride and dimethyl formamide fol-
lowed by hydrolysis. Amino-condensation of 3-substituted-
4-amino-5-mercapto-1,2,4-triazoles (1) with different
3-substituted-1H-pyrazole carbaldehydes (2) in absolute
ethanol medium in the presence of catalytic amount of
concentrated sulphuric acid yielded 5-substituted-4-[(3-
Anticancer activity
Evaluation of anticancer activity was carried out in human
breast cancer (MCF-7) cells, purchased from National
Cancer Center for Cell Science, Pune, India. The cells were
cultured in Dulbecco’s modified Eagles medium (DMEM)-
containing 10 % fetal bovine serum (FBS) at 37 °C in an
atmosphere containing 5 % CO2. Unless otherwise men-
tioned, all the chemicals used in this study were from
Sigma-Aldrich, USA.
123

Med Chem Res
N
N
SH
R1
N
CHO
N
N
N
N
O
R O
Conc. H2SO4
EtOH
R
SH
R1
N
+
N
H
H2N
N
N
H
1a-e
2a-c
3a-o
SHCH2COOH
N
N
SH
R O
N
N
O
NH
N
S
R1
4a-o
R = Phenyl, 2-methylphenyl, 4-methylphenyl, 1-naphthyl, 2-naphthyl
R1 = 4-chlorophenyl, 4-flurophenyl, 4-methoxyphenyl
Scheme 1 Synthetic route for the triazolothiazolidinones
Scheme 2 Plausible
mechanism for the formation of
thiazolidinone
N
Pyz
Pyz
Tzl
Pyz
S
S
Step-1
Step-2
-H2O
Tzl
NH
N
Tzl
SH
O
O
OH
OH
C
O
N
N
N
R1
SH
N
O
N
H
R
123

Med Chem Res
MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
tetrazolium bromide assay (Mosmann, 1983; Kavitha et al.,
2009)
Comet assay (Single cell gel electrophoresis) (Kavitha
et al., 2009; Singh, 2000)
To assess the genotoxic effect of the selected thiazolidin-4-
ones comet assay was performed in MCF-7 cells. The three
thiazolidin-4-ones, 4b, 4d, and 4f which showed good
cytotoxicity in the MTT assay were selected for this study.
MCF-7 (1 9 106) cells were treated with three different
concentrations, 10, 25, and 50 lg/mL of thiazolidin-4-ones
for 24 h. The cells were then washed and 200 lL of cell
suspension in low melting agarose (LMA) was layered on
to the labelled slides precoated with agarose (1.5 %). The
slides were placed on ice for 10 min and submerged in
lysis buffer (2.5 % NaCl, 100 mM EDTA, 10 mM Tris,
10 % DMSO, and 1 % Troton X—100) at pH 10 at 4 °C
for more than 1 h. The slides were then equilibrated in
alkaline buffer (30 mM NaOH, 1 mM EDTA) at pH 13 at
4 °C, electrophoresed at 0.86 V/cm at 4 °C, neutralized,
washed, and dried. At the time of capturing the images, the
slides were stained with ethidium bromide (EtBr, 150 lL
1X) and cover slips were placed over them. For visuali-
zation of DNA-damage EtBr-stained slides were observed
under 209 objectives of a fluorescent microscope (Olym-
pus BX-51, Japan). The images of 50–100 randomly
selected cells were captured per slide using a CCD camera.
The images of comet assay for control, cells treated with
doxorubicin (0.1 lM, 54 lg/mL), 4b (50 lg/mL), 4d
(50 lg/mL), and 4f (50 lg/mL) are shown in Fig. 1. Slides
were analysed for parameters like tail length (TL), and
olive tail moment (OTM) using image analyzer CASP
software version 1.2.2. The results of the assay for TL and
OTM are shown in Figs. 2 and 3, respectively.
Ten of the randomly selected synthesized thiazolidin-4-
ones were screened for their anticancer activities at Man-
ipal College of Pharmaceutical Sciences, Manipal Uni-
versity, India. The stock solution of thiazolidin-4-ones to
determine their cytotoxic effect were prepared in 10 %
dimethyl sulphoxide (DMSO) and further diluted in phos-
phate buffer saline (PBS) before use. The final concentra-
tion of DMSO in the solution was less than 0.1 %. Cells
were seeded in duplicates in 96-well plates at
1 9 104 cells/well. After 24 h, the thiazolidin-4-ones were
added at a concentration of 0.1, 1, 10, and 100 lg/mL and
incubated for another 24 h. 5 9 10-3 mol of MTT reagent
was added and incubated for additional 4 h. The purple
formazan crystals were then dissolved in 0.1 mL of
hydrochloric acid (0.4 N):isopropanol (1:24). Cells grown
in culture media with appropriate concentration of DMSO
were used as control. Doxorubicin was used as the standard
drug. The optical density of each well was measured at
570 nm in an ELISA plate reader. The results were
reported as percentage survival of the cells when compared
to that of the untreated control cells standard deviation
(Table 1).
The IC50 for the standard drug doxorubicin was found to
be 18 lg/mL. Among the ten new thiazolidin-4-ones
screened for cytotoxicity in MTT assay, 4b, 4d, and 4f
exhibited excellent cytotoxicity with IC50 values of 30, 22,
and 29 lg/mL. The methyl group in the ortho position
probably might have increased the activity of 4d and 4f.
The presence of methyl groups increases the lipophilicity,
which can drastically modify the bioavailability of the
compound and thus its efficacy. 4j, 4l, and 4m with the
bulky naphthyl groups displayed least cytotoxic activity.
head extent
Tail length ¼ Tail extent þ
2
Olive tail moment ¼ Tail length ꢁ %Tail DNA
Table 1 Cytotoxic activity data of thiazolidin-4-ones in MTT assay
Compound
no.
Vehicle control
(% survival)
0.1 lg/mL
(% survival)
1 lg/mL
(% survival)
10 lg/mL
(% survival)
100 lg/mL
(% survival)
IC50 lg/mL
4b
4c
4d
4e
4f
100 5.99
100 7.53
100 5.90
100 5.90
100 7.50
100 5.99
100 5.90
100 2.09
100 7.50
100 7.50
65.92 4.74
100 10.45
70.0 4.60
81.4 6.20
81.5 10.4
80.84 2.6
95.05 4.8
100.8 2.1
99.7 10.2
100 7.50
69.43 8.41
100 5.10
80.7 5.0
83.1 4.60
87.0 5.40
74.66 4.7
95.38 9.4
70.5 3.70
100 3.70
100 3.60
76.47 4.65
96.80 1.8
67.57 3.4
92.5 5.70
84.7 1.70
87.5 8.50
90.2 5.2
33.60 1.77
46.45 6.50
13.2 1.40
62.1 8.40
25.4 1.80
71.4 8.70
43.67 5.5
51.8 10.3
50.7 4.30
96.5 5.40
30
85
22
[100
29
4h
4i
[100
78
4j
60.3 7.90
81.4 3.08
99.85 2.54
100
100
[100
4m
4n
123

Med Chem Res
Fig. 1 Detection of DNA
damage in MCF-7 cells. Treated
cells (24 h) were layered over
agarose gel, lysed,
electrophoresed in alkaline
buffer and stained with
propidium iodide. Control cells
were treated with DMSO alone.
The DNA fragmentation
resulting in a comet-like
appearance is seen control and
in cells treated with
doxorubicin, 4b, 4d, and 4f
In the comet assay, the images of cells treated with
doxorubicin, 4b, 4d, and 4f showed the formation of comets.
No comet pattern was observed in the control cells. There
was dose-dependent increase in tail length and OTM when
treated with 4b, 4d, and 4f. 4d presented maximum apoptotic
DNA damage among the three thiazolidin-4-ones studied,
which was in accordance with its maximum cytotoxicity as
seen in MTT assay. None of the thiazolidin-4-ones exhibited
apoptotic DNA damage to the extent of doxorubicin. The
quantified increase in DNA damage suggested that all three
thiazolidin-4-ones induced dose-dependent fragmentation
of chromosomal DNA leading to apoptosis.
to decolorize in the presence of antioxidants. DPPH radical
scavenging is mediated by transfer of hydrogen atom. The
DPPH radical contains an odd electron, which is responsible
for the absorbance at 517 nm and also for visible deep
purple color. When DPPH accepts an electron donated by
an antioxidant compound, the DPPH is decolorized which
can be quantitatively measured from the changes in absor-
bance. 100 lL of various concentrations of 4b, 4d, and 4f
were added to respective wells of a 96-well micro plate.
Equal amount of DPPH was also added to each well to make
up a final volume of 200 lL. After 20 min incubation in the
dark, the ability of the three thazolidin-4-ones to scavenge
the free radical DPPH, was measured by recording the
absorbance at 517 nm using an ELISA plate recorder.
Experiment was performed in triplicates and average values
were considered. An equal amount of methanol and DPPH
was added to the control wells. Vitamin C (Ascorbic acid),
the antioxidant most made known for its potential benefits
to cancer patients, was used as the standard. Results of the
DPPH assay are shown in Table 2.
Antioxidant studies
DPPH radical scavenging assay (Sreejayan and Rao,
1996; Vaijanathappa et al., 2008)
The DPPH (1,1-diphenyl-2-picryl hydrazide) antioxidant
assay is based on the ability of DPPH, a stable free radical,
123

Med Chem Res
Table 2 Results of antioxidant studies of thiazolidin-4-ones
A
400
300
200
100
0
a
Compounds
IC50 (in lg/mL)
DPPH
ABTS
Asc. A
4b
18.74 1.16
27.16 2.15
31.52 1.98
46.95 2.42
31.53 2.85
143.67 5.70
73.03 3.91
165.78 6.44
a,b
a,b
a,b
a,b
4d
a,b
a,b
4f
a,b
Asc. A Ascorbic acid (standard)
a,b
a,b
ABTS radical scavenging assay (Sreejayan and Rao, 1996;
Vaijanathappa et al., 2008)
Sham Control
4b (50 µg/mL)
4f (10 µg/mL)
DOX (0.1µM)
4d (10 µg/mL)
4f (25 µg/mL)
4b (10 µg/ml)
4d (25 µg/mL)
4f (50 µg/mL)
4b (25 µg/mL)
4d (50 µg/mL)
ABTS is chemically 2,2-azino bis 3-ethyl benzo-thiazoline-
6-sulphonic acid. The reduction of this radical by 4b, 4d,
and 4f was measured at 690 nm. The electron transfer
capability of the three thiazolidin-4-ones was studied using
ABTS radical scavenging assay. In a 96-welled microtitre
plate, 40 lL of the thiazolidin-4-ones/ascorbic acid,
200 lL of methanol, and 30 lL of ABTS solution were
added. The plate was then incubated at 37 °C for 20 min
after which the absorbance was measured at 690 nm using
an ELISA plate reader. Sample blank and control were also
taken. The experiment was performed in triplicates and
average values were considered. The results of ABTS assay
is shown in Table 2.
Fig. 2 Graph comparing the effect of thiazolidin-4-ones on the tail
length in comet assay. There was a concentration-dependent increase
in the apoptotic DNA fragmentation and hence an increase in tail
length in all three thiazolidin-4-ones. The extent of damage caused by
doxorubicin (0.1 lM) was more when compared to the three
thiazolidinon-4-ones, 4b, 4d, and 4f. 4d caused maximum DNA
damage in the comet assay
B
100
a
% scavenging of ABTS
ꢀ
80
ꢁ
Absorbance of control ꢂ Absorbance of test sample
¼
Absorbance of control
a,b
60
40
20
ꢁ 100
a,b
a,b
a,b
a,b
In DPPH and ABTS assay, none of the three thiazolidin-
4-ones were as potent as the standard compound ascorbic
acid. 4d was found to show moderate antioxidant
properties with comparatively low IC50 values. As the
IC50 value of 4d in DPPH assay was lower than that in
ABTS assay, the mechanism of antioxidant action is
presumed to be through hydrogen transfer.
a,b
b
b
a,b
0
Sham Control
DOX (0.1µM)
4d (10 µg/mL)
4f (25 µg/mL)
4b (10 µg/ml)
4d (25 µg/mL)
4f (50 µg/mL)
4b (25 µg/mL)
4d (50 µg/mL)
4b (50 µg/mL)
4f (10 µg/mL)
Fig. 3 Graph relating the effect of thiazolidin-4-ones on the olive
tail moment in comet assay. There was a concentration-dependent
increase in the OTM in all three thiazolidin-4-ones. The extent of
damage caused by doxorubicin (0.1 lM) was more when compared to
the three thiazolidinon-4-ones, 4b, 4d, and 4f. 4d exhibited maximum
OTM in the comet assay
Conclusion
In this study, a series of fifteen new thiazolidin-4-ones were
synthesized by the cyclo-condensation reaction between
Schiff bases and thioglycollic acid. The different spectral
techniques and the elemental analysis confirmed the
structure of the compounds. Three thiazolidin-4-ones, 4b,
4d, and 4f exhibited excellent cytotoxic activity in MCF-7
cell lines with low IC50 values. The comet assay showed
the extent of apoptotic DNA damage. 4d exhibited
% scavenging of DPPH
ꢀ
ꢁ
Absorbance of control ꢂ Absorbance of test
Absorbance of control
ꢁ 100
¼
123

Med Chem Res
maximum DNA fragmentation and presented moderate
antioxidant properties in DPPH and ABTS assays. The
chlorine atom might have added to the potency of 4d as it
produces simultaneously an increase in lipophilicity and an
electron attracting effect. The presence of chlorine atom
and a methyl group in the ortho position has drastically
increased the anticancer activity of 4d, as compared to the
bulky naphthyl groups.
NMR (400 MHz, DMSO-d6): d 5.02 (s, 2H, CH2 of thia-
zolidinone ring), d 5.31 (s, 1H, CH of thiazolidinone ring),
d 5.62 (s, 2H, OCH2), d 6.94 (1H, pyrazole C–H), d 7.1–7.9
(m, 9H, Ar.H), d 11.68 (s, 1H, Pyrazole N–H), d 13.78 (brs,
1H, SH); MS (m/z): 468 (M?); Anal. Calcd. for
C21H17FN6O2S2: C, 53.85; H, 3.63; N, 17.95; found: C,
54.01; H, 3.54; N, 17.85.
3-(3-mercapto-5-(phenoxymethyl)-4H-1,2,4-triazol-4-yl)-
2-(3-(4-methoxyphenyl)-1H-pyrazol-4-yl)thiazolidin-4-one
(4c)
Experimental
General procedure for the synthesis of 2-(3-substituted-
1H-pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-
triazol-4-yl)-1,3-thiazolidin-4-one (4a–o)
Yellow solid (65 %); m.p. 138–140 °C; IR (KBr, mmax
cm-1): 3,100–3,200 (pyrazole N–H str.), 3090 (Ar. C–H
str.), 2950, 2860 (methyl C–H str.), 1,729 (C=O of thiazo-
lidinone), 1,507 (Ar.C=C str.), 1018, 1249 (Ar.C–O–C), 610
([C–S–C\str.); 1H NMR (400 MHz, DMSO-d6): d 3.27 (s,
3H, OCH3), d 5.02 (s, 2H, CH2 of thiazolidinone ring), d 5.32
(s, 1H, CH of thiazolidinone ring), d 5.62 (s, 2H, OCH2), d
6.95 (1H, pyrazole C–H), d 7.1–7.8 (m, 9H, Ar.H), d 11.81
(brs, 1H, Pyrazole N–H), d 13.79 (brs, 1H, SH); MS (m/z):
480 (M?); Anal. Calcd. for C22H20N6O3S2: C, 55.00; H,
4.17; N, 17.50; found: C, 55.19; H, 4.01; N, 17.29.
0.01 mol of 5-substituted-4-(3-substituted-1H-pyrazol-4-yl
methylidene) amino]-2H-1,2,4-triazole-3-thione and 0.01
mol of thioglycolic acid in dimethyl formamide were
allowed to undergo nucleophilic cyclo-condensation under
reflux in presence of 0.05 g ZnCl2 for 24 h. Excess of the
solvent was distilled off and the reaction mixture was
poured into ice cold water. The solid separated was col-
lected, washed with NaHCO3 solution and water. The
precipitate of 2-(3-substituted-1H-pyrazol-4-yl)-3-(3-sub-
stituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-4-one
obtainedwas dried and recrystallized from chloroform to
petroleum ether mixture.
2-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
(o-tolyloxymethyl)-4H-1,2,4-triazol-4-yl)thiazolidin-4-one
(4d)
Yellow solid (73 %); m.p. 156–158 °C; IR (KBr, mmax
cm-1): 3,100–3,200 (pyrazole N–H str.), 3,190 (Ar. C–H
str.), 2950, 2860 (methyl C–H str.), 1,733 (C=O of thia-
zolidinone), 1,506 (Ar.C=C str.), 1018, 1244 (Ar.C–O–C),
2-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
(phenoxymethyl)-4H-1,2,4-triazol-4-yl)thiazolidin-4-one
(4a)
1
608 ([C–S–C\str.); H NMR (400 MHz, DMSO-d6): d
Yellow solid (75 %); m.p. 162–164 °C; IR (KBr,
mmax cm-1): 3,100–3,200 (pyrazole N–H str.), 3,185 (Ar.
C–H str.), 1,731 (C=O of thiazolidinone), 1,498 (Ar.C=C
str.), 1016, 1245 (Ar.C–O–C), 608 ([C–S–C\str.); 1H
NMR (400 MHz, DMSO-d6): d 5.01 (s, 2H, CH2 of thia-
zolidinone ring), d 5.33 (s, 1H, CH of thiazolidinone ring),
d 5.62 (s, 2H, OCH2), d 6.94 (s, 1H, pyrazole C–H), d
7.1–7.8 (m, 9H, Ar.H), d 11.8 (s, 1H, Pyrazole N–H), d
13.79 (brs, 1H, SH); MS (m/z): 484 (M?); Anal. Calcd. for
C21H17ClN6O2S2: C, 52.01; H, 3.51; N, 17.34; found: C,
52.15; H, 3.36; N, 17.49.
2.25 (s, 3H, CH3), d 5.02 (s, 2H, CH2 of thiazolidinone
ring), d 5.33 (s, 1H, CH of thiazolidinone ring), d 5.6 (s,
2H, OCH2), d 6.95 (1H, pyrazole C–H), d 7.1–7.9 (m, 8H,
Ar.H), d 11.68 (s, 1H, Pyrazole N–H), d 13.79 (brs, 1H,
SH); MS (m/z): 498 (M?); Anal. Calcd. for C22H19
ClN6O2S2: C, 52.96; H, 3.81; N, 16.85; found: C, 53.08; H,
3.75; N, 17.07.
2-(3-(4-fluorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
(o-tolyloxymethyl)-4H-1,2,4-triazol-4-yl)thiazolidin-4-one
(4e)
2-(3-(4-fluorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
(phenoxymethyl)-4H-1,2,4-triazol-4-yl)thiazolidin-4-one
(4b)
Yellow solid (71 %); m.p. 142–144 °C; IR (KBr,
mmax cm-1): 3,100–3,200 (pyrazole N–H str.), 3,185 (Ar.
C–H str.), 2950, 2862 (methyl C–H str.), 1,730 (C=O of
thiazolidinone), 1,506 (Ar.C=C str.), 1019, 1248 (Ar.C–O–
C), 605 ([C–S–C\str.); 1H NMR (400 MHz, DMSO-d6): d
2.25 (s, 3H, CH3), d 5.02 (s, 2H, CH2 of thiazolidinone
ring), d 5.34 (s, 1H, CH of thiazolidinone ring), d 5.61 (s,
2H, OCH2), d 6.94 (1H, pyrazole C–H), d 7.1–7.9 (m, 8H,
Yellow solid (67 %); m.p. 164–166 °C; IR (KBr,
mmax cm-1): 3,100–3,200 (pyrazole N–H str.), 3,180 (Ar.
C–H str.), 1,732 (C=O of thiazolidinone), 1,508 (Ar.C=C
str.), 1018, 1240 (Ar.C–O–C), 610 ([C–S–C\str.); 1H
123

Med Chem Res
Ar.H), d 11.90 (s, 1H, Pyrazole N–H), d 13.78 (brs, 1H,
SH); MS (m/z): 482 (M?); Anal. Calcd. for C22H19
FN6O2S2: C, 54.77; H, 3.94; N, 17.43; found: C, 54.89; H,
3.81; N, 17.52.
C22H19FN6O2S2: C, 54.77; H, 3.94; N, 17.43; found: C,
54.67; H, 4.05; N, 17.34.
3-(3-mercapto-5-(p-tolyloxymethyl)-4H-1,2,4-triazol-4-yl)-
2-(3-(4-methoxyphenyl)-1H-pyrazol-4-yl)thiazolidin-4-one
(4i)
3-(3-mercapto-5-(o-tolyloxymethyl)-4H-1,2,4-triazol-4-yl)-
2-(3-(4-methoxyphenyl)-1H-pyrazol-4-yl)thiazolidin-4-one
(4f)
Yellow solid (68 %), m.p. 160–162 °C, IR (KBr,
mmax cm-1): 3,100–3,200 (pyrazole N–H str.), 3,185 (Ar.
C–H str.), 2960, 2850 (methyl C–H str.), 1,730 (C=O of
thiazolidinone), 1,505 (Ar.C=C str.), 1019, 1250 (Ar.C–O–
C), 612 ([C–S–C\str.); 1H NMR (400 MHz, DMSO-d6): d
2.23 (s, 3H, CH3), d 3.32 (s, 3H, OCH3), d 5.01 (s, 2H, CH2
of thiazolidinone ring), d 5.33 (s, 1H, CH of thiazolidinone
ring), d 5.61 (s, 2H, OCH2), d 6.96 (1H, pyrazole C–H), d
7.1–7.8 (m, 8H, Ar.H), d 11.65 (s, 1H, Pyrazole N–H), d
13.80 (brs, 1H, SH); MS (m/z): 494 (M?); Anal. Calcd. for
C23H22N6O3S2: C, 55.87; H, 4.45; N, 17.00; found: C,
55.72; H, 4.29; N, 16.87.
Yellow solid (70 %); m.p. 174–176 °C; IR (KBr,
mmax cm-1): 3,100–3,200 (pyrazole N–H str.), 3,170 (Ar.
C–H str.), 2960, 2890 (methyl C–H str.), 1,740 (C=O of
thiazolidinone), 1,505 (Ar.C=C str.), 1017, 1292 (Ar.C–O–
C), 600 ([C–S–C\str.); 1H NMR (400 MHz, DMSO-d6): d
2.22 (s, 3H, CH3), d 3.29 (s, 3H, OCH3), d 5.03 (s, 2H, CH2
of thiazolidinone ring), d 5.31 (s, 1H, CH of thiazolidinone
ring), d 5.61 (s, 2H, OCH2), d 6.84 (1H, pyrazole C–H), d
7.1–7.8 (m, 8H, Ar.H), d 11.55 (s, 1H, Pyrazole N–H),
13.80 (brs, 1H, SH); MS (m/z): 494 (M?); Anal. Calcd. for
C23H22N6O3S2: C, 55.87; H, 4.45; N, 17.00; found: C,
56.01; H, 4.31; N, 17.13.
2-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
((naphthalen-1-yloxy)methyl)-4H-1,2,4-triazol-4-
yl)thiazolidin-4-one (4j)
2-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
(p-tolyloxymethyl)-4H-1,2,4-triazol-4-yl)thiazolidin-4-one
(4g)
Yellow solid (71 %); m.p. 176–178 °C; IR (KBr,
mmax cm-1): 3,100–3,200 (pyrazole N–H str.), 3,112 (Ar.
C–H str.), 1,734 (C=O of thiazolidinone), 1,504 (Ar.C=C
str.), 1018, 1245 (Ar.C–O–C), 825 (Ar.C–H def.), 730, 820,
842 (naphthalene C–H def.), 608 ([C–S–C\str.); 1H NMR
(400 MHz, DMSO-d6): d 5.03 (s, 2H, CH2 of thiazolidi-
none ring), d 5.34 (s, 1H, CH of thiazolidinone ring), d 5.62
(s, 2H, OCH2), d 6.92 (1H, pyrazole C–H), d 7.1–8.1 (m,
11H, Ar.H), d 11.62 (s, 1H, Pyrazole N–H), d 13.79 (brs,
1H, SH); MS (m/z): 534 (M?); Anal. Calcd. for
C25H19ClN6O2S2: C, 56.13; H, 3.55; N, 15.72; found: C,
56.25; H, 3.45; N, 15.60.
Yellow solid (71 %); m.p. 182–184 °C; IR (KBr, mmax
cm-1): 3,100–3,200 (pyrazole N–H str.), 3,147 (Ar. C–H
str.), 2930, 2860 (methyl C–H str.), 1,737 (C=O of thia-
zolidinone), 1,510 (Ar.C = C str.), 1021, 1238 (Ar.C–O–
C), 610 ([C–S–C\str.); 1H NMR (400 MHz, DMSO-d6): d
2.23 (s, 3H, CH3), d 5.01 (s, 2H, CH2 of thiazolidinone
ring), d 5.33 (s, 1H, CH of thiazolidinone ring), d 5.6 (s,
2H, OCH2), d 6.95 (1H, pyrazole C–H), d 7.1–7.8 (m, 8H,
Ar.H), d 11.68 (s, 1H, Pyrazole N–H), d 13.81 (brs, 1H,
SH); MS (m/z): 498 (M?); Anal. Calcd. for C22H19
ClN6O2S2: C, 52.96; H, 3.81; N, 16.85; found: C, 52.84; H,
3.77; N, 16.93.
2-(3-(4-fluorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
((naphthalen-1-yloxy)methyl)-4H-1,2,4-triazol-4-
yl)thiazolidin-4-one (4k)
2-(3-(4-fluorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
(p-tolyloxymethyl)-4H-1,2,4-triazol-4-yl)thiazolidin-4-one
(4h)
Yellow solid (68 %); m.p. 180–182 °C; IR (KBr, mmax
cm-1): 3,100–3,200 (pyrazole N–H str.), 3,095 (Ar. C–H
str.), 1,732 (C=O of thiazolidinone), 1,508 (Ar.C=C str.),
1019, 1248 (Ar.C–O–C), 824 (Ar.C–H def.), 750, 830, 844
(naphthalene C–H def.), 610 ([C–S–C\str.); 1H NMR
(400 MHz, DMSO-d6): d 5.01 (s, 2H, CH2 of thiazolidi-
none ring), d 5.33 (s, 1H, CH of thiazolidinone ring), d 5.62
(s, 2H, OCH2), d 6.94 (1H, pyrazole C–H), d 7.1–7.9 (m,
11H, Ar.H), d 11.75 (s, 1H, Pyrazole N–H), d 13.78 (brs,
1H, SH); MS (m/z): 518 (M?); Anal. Calcd. for
C25H19FN6O2S2: C, 57.92; H, 3.67; N, 16.22; found: C,
58.03; H, 3.74; N, 16.35.
Yellow solid (71 %); m.p. 174–176 °C; IR (KBr, mmax
cm-1): 3,100–3,200 (pyrazole N–H str.), 3,160 (Ar. C–H
str.), 2850, 2930 (methyl C–H str.), 1,732 (C=O of thia-
zolidinone), 1,507 (Ar.C=C str.), 1011, 1242 (Ar.C–O–C),
1
608 ([C–S–C\str.); H NMR (400 MHz, DMSO-d6): d
2.25 (s, 3H, CH3), d 5.05 (s, 2H, CH2 of thiazolidinone
ring), d 5.35 (s, 1H, CH of thiazolidinone ring), d 5.63 (s,
2H, OCH2), d 6.92 (1H, pyrazole C–H), d 7.1–7.7 (m, 8H,
Ar.H), d 11.65 (s, 1H, Pyrazole N–H), d 13.78 (brs, 1H,
SH); MS (m/z): 482 (M?); Anal. analysis Calcd. for
123

Med Chem Res
3-(3-mercapto-5-((naphthalen-1-yloxy)methyl)-4H-1,2,4-
triazol-4-yl)-2-(3-(4-methoxyphenyl)-1H-pyrazol-4-
yl)thiazolidin-4-one (4l)
3-(3-mercapto-5-((naphthalen-2-yloxy)methyl)-4H-1,2,4-
triazol-4-yl)-2-(3-(4-methoxyphenyl)-1H-pyrazol-4-
yl)thiazolidin-4-one (4o)
Yellow solid (72 %); m.p. 145 °C; IR (KBr, mmax cm-1):
3,100–3,200 (pyrazole N–H str.), 3,118 (Ar. C–H str.),
1,733 (C=O of thiazolidinone), 2950, 2860 (methyl C–H
str.), 1,505 (Ar.C=C str.), 1015, 1242 (Ar.C–O–C), 820
(Ar.C–H def.), 752, 828, 840 (naphthalene C–H def.), 609
([C–S–C\str.); 1H NMR (400 MHz, DMSO-d6): d 3.29 (s,
3H, OCH3), d 5.03 (s, 2H, CH2 of thiazolidinone ring), d
5.32 (s, 1H, CH of thiazolidinone ring), d 5.62 (s, 2H,
OCH2), d 6.93 (1H, pyrazole C–H), d 7.1–8.1 (m, 11H,
Ar.H), d 11.45 (s, 1H, Pyrazole N–H), d 13.79 (brs, 1H,
SH); MS (m/z): 530 (M?); Anal. Calcd. for C26H22N6O3S2:
C, 58.87; H, 4.15; N,15.85; found: C, 58.67; H, 4.22; N,
15.79.
Yellow solid (66 %); m.p. 203–205 °C; IR (KBr,
mmax cm-1): 3,100–3,200 (pyrazole N–H str.), 3,170 (Ar.
C–H str.), 2950, 2860 (methyl C–H str.), 1,733 (C=O of
thiazolidinone), 1,505 (Ar.C = C str.), 1019, 1246 (Ar.C–
O–C), 820 (Ar.C–H def.), 752, 825, 846 (naphthalene C–H
1
def.), 608 ([C–S–C\str.); H NMR (400 MHz, DMSO-
d6): d 3.28 (s, 3H, OCH3), d 5.04 (s, 2H, CH2 of thiazo-
lidinone ring), d 5.33 (s, 1H, CH of thiazolidinone ring), d
5.61 (s, 2H, OCH2), d 6.95 (1H, pyrazole C–H), d 7.1–8.1
(m, 11H, Ar.H), d 11.65 (s, 1H, Pyrazole N–H), d 13.79
(brs, 1H, SH); MS (m/z): 530 (M?); Anal. Calcd. for
C26H22N6O3S2: C, 58.87; H, 4.15; N, 15.85; found: C,
59.02; H, 3.98; N, 15.99.
Acknowledgments The authors are thankful to the Head-SIF,
Indian Institute of Science, Bangalore for providing NMR and mass
spectral data. AMI is thanks Department of Atomic Energy, Board for
Research in Nuclear Sciences, Government of India for the ‘Young
Scientist’ award.
2-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
((naphthalen-2-yloxy)methyl)-4H-1,2,4-triazol-4-
yl)thiazolidin-4-one (4m)
Yellow solid (69 %); m.p. 217–219 °C; IR (KBr, mmax
cm-1): 3,100–3,200 (pyrazole N–H str.), 3,110 (Ar. C–H
str.), 1,735 (C=O of thiazolidinone), 1,507 (Ar.C=C str.),
1018, 1240 (Ar.C–O–C), 820 (Ar.C–H def.), 750, 820, 840
(naphthalene C–H def.), 606 ([C–S–C\str.); 1H NMR
(400 MHz, DMSO-d6): d 5.03 (s, 2H, CH2 of thiazolidi-
none ring), d 5.35 (s, 1H, CH of thiazolidinone ring), d 5.63
(s, 2H, OCH2), d 6.93 (1H, pyrazole C–H), d 7.1–8.1 (m,
11H, Ar.H), d 11.64 (s, 1H, Pyrazole N–H), d 13.78 (brs,
1H, SH); MS (m/z): 534 (M?); Anal. Calcd. for
C25H19ClN6O2S2: C, 56.13; H, 3.55; N, 15.72; found: C,
55.97; H, 3.49; N, 15.63.
References
Amir M, Azam F (2004) Synthesis and biological evaluation of some
4-thiazolidinones. Indian J Heterocycl Chem 14:119–122
Bandgar PB, Gawande SS, Bodade RG, Gawande NM, Khobragade
CN (2009) Synthesis and biological evaluation of a novel series
of pyrazole chalcones as anti-inflammatory, antioxidant and
antimicrobial agents. Bioorg Med Chem 17:8168–8173
Bandgar PB, Gawande SS, Bodade RG, Totre JV, Khobragade CN
(2010) Synthesis and biological evaluation of simple methoxy-
lated chalcones as anticancer, anti-inflammatory and antioxidant
agents. Bioorg Med Chem 18:1364–1370
Brueggemeier RW, John CH, Edgar SD (2004) Aromatase inhibitors
in the treatment of breast cancer. Endocrine Rev 26:331–345
Chandrakantha B, Isloor AM, Shetty P, Isloor S, Malladi S, Fun HK
(2011) Synthesis, characterization and antimicrobial activity of
novel ethyl 1-(N-substituted)-5-phenyl-1H-pyrazole-4-carboxyl-
ate derivatives. Med Chem Res. doi:10.1007/s00044-011-9796-9
Demirbas N, Karaoglu SA, Demirbas A, Sanack K (2004) Synthesis
and antimicrobial activities of some new 1-(5-phenylamino-
[1,3,4]thiadiazol-2-yl)methyl-5-oxo-[1,2,4]triazole and 1-(4-phe-
2-(3-(4-fluorophenyl)-1H-pyrazol-4-yl)-3-(3-mercapto-5-
((naphthalen-2-yloxy)methyl)-4H-1,2,4-triazol-4-
yl)thiazolidin-4-one (4n)
Yellow solid (70 %); m.p. 218–220 °C; IR (KBr, mmax
cm-1): 3,100–3,200 (pyrazole N–H str.), 3,195 (Ar. C–H
str.), 1,731 (C=O of thiazolidinone), 1,504 (Ar.C=C str.),
1019, 1244 (Ar.C–O–C), 825 (Ar.C–H def.), 752, 820, 845
(naphthalene C–H def.), 610 ([C–S–C\str.); 1H NMR
(400 MHz, DMSO-d6): d 5.02 (s, 2H, CH2 of thiazolidi-
none ring), d 5.32 (s, 1H, CH of thiazolidinone ring), d 5.63
(s, 2H, OCH2), d 6.95 (1H, pyrazole C–H), d 7.1–7.9 (m,
11H, Ar.H), d 11.78 (s, 1H, Pyrazole N–H), d 13.78 (brs,
1H, SH); MS (m/z): 518 (M?); Anal. Calcd. for
C25H19FN6O2S2: C, 57.92; H, 3.67; N, 16.22; found: C,
57.82; H, 3.53; N, 15.99.
nyl-5-thioxo-[1,2,4]
derivatives. Eur J Med Chem 39:793–804
triazole-3-yl)methyl-5-oxo[1,2,4]triazole
Dobrowsky W, Huigol NG, Jayatilake RS, Kizilbash NI, Okkan S,
Kagiya TV, Tatsuzaki H (2005) AK-2123 (Sanazol) as a
radiation sensitizer in the treatment of stage III cancer cervix:
initial results of an IAEA multicentre randomized trial. J Cancer
Res Ther 1:75–78
Hafez HN, El-Gazzar ABA (2009) Synthesis and antitumor activity of
substituted triazolo[4,3-a]pyrimidin-6-sulfonamide with an
incorporated thiazolidinone moiety. Bioorg Med Chem Lett
19:4143–4147
Holla BS, Poojary KN, Rao BS, Shivananda MK (2002) New bis-
aminomercaptotriazoles and bis-triazolothiadiazoles as possible
anticancer agents. Eur J Med Chem 37:511–517
123

Med Chem Res
Ibrahim DA (2009) Synthesis and biological evaluation of 3,6-
disubstituted [1,2,4] triazolo[3,4-b][1,3,4]thiadiazole derivatives
as a novel class of potential anti-tumor agents. Eur J Med Chem
44:2776–2781
Isloor AM, Kalluraya B, Shetty P (2009) Regioselective reaction:
synthesis, characterization and pharmacological studies of some
new Mannich bases derived from 1,2,4-triazoles. Eur J Med
Chem 44:3784–3787
Kavitha CV, Nambiar M, Ananda Kumar CS, Choudhari B,
Muniyappa K, Rangappa KS, Raghavan SC (2009) Novel
derivatives of spirohydantoin induce growth inhibition followed
by apoptosis in leukemia cells. Biochem Pharmacol 77:348–363
Selvi G, Rajendran SP (2007) Synthesis of 2-[30(20-chloroquinolinyl)-
3-carbethoxymethyl]-4-thiazolidinones. Indian J Het Chem 17:
201–202
Siddiqui N, Deepanjali, Md Arshad F, Rana A (2007) Synthesis and
anticonvulsant screening of 2-(substituted aryl)-3-(4H-1,2,4-
triazol-4-yl)-1,3-thiazolidinon-4-ones. Indian J Het Chem 16:
403–404
Singh NP (2000) Microgels for estimation of DNA strand breaks,
DNA protein cross links and apoptosis. Mutation Res 455:
111–127
Sreejayan N, Rao MN (1996) Free radical scavenging activity of
curcuminoids. Drug Res 46:169–171
Lee T, Lau T, Ng
I
(2002) Doxorubicin-induced apoptosis
Sunil D, Isloor AM, Shetty P, Chandrakantha B, Satyamoorthy K
(2011) Synthesis, characterization and in vitro cytotoxic prop-
erties of some new Schiff and Mannich bases in Hep G2 cells.
Med Chem Res 20:1024–1032
Swamy SN, Basappa, Priya BS, Prabhuswamy B, Doreswamy BH,
Prasad JS, Rangappa KS (2006) Synthesis of pharmaceutically
important condensed heterocyclic 4,6-disubstituted-1,2,4-triaz-
olo-1,3,4-thiadiazole derivatives as antimicrobials. Eur J Med
Chem 41:531–538
Vaijanathappa J, Badami S, Bhojraj S (2008) In vitro antioxidant
activity of Enicostemmaaxillare. J Health Sci 54:524–528
Vijesh AM, Isloor AM, Prabhu V, Ahmad S, Malladi S (2010)
Synthesis, characterization and anti-microbial studies of some
and chemosensitivity in hepatoma cell lines. Cancer Chemother
Pharmacol 49:78–86
Malladi S, Isloor AM, Isloor S, Akhila DS (2011a) Synthesis,
characterization and ntibacterial activity of some new pyrazole
based Schiff bases. Arabian J Chem. doi:10.1016/j.arabjc.
2011.10.009
Malladi S, Isloor AM, Shetty P, Fun HK, Telkar S, Mahmood R,
Isloor N (2011b) Synthesis and anti-inflammatory evaluation of
some new 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiaz-
oles bearing pyrazole moiety. Med Chem Res. doi:10.1007/
s00044-011-9865-0
Mathew V, Keshavayya J, Vaidya VP, Giles D (2007) Studies on
synthesis and pharmacological activities of 3,6-disubstituted-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro ana-
logues. Eur J Med Chem 42:823–840
novel 2,4-disubstituted thiazoles. Eur
5460–5464
J Med Chem 45:
Vijesh AM, Isloor AM, Telkar S, Peethambar SK, Rai S, Isloor N
(2011a) Synthesis, characterization and antimicrobial studies of
some new pyrazole incorporated imidazole derivatives. Eur J
Med Chem 46:3531–3536
Mosmann T (1983) Rapid colorimetric assay for cellular growth and
survival: application to proliferation and cytotoxic assays.
Immunol Methods 65:55–63
Padmavathi V, Reddy GS, Padmaja A, Kondaiah P, Ali-Shazia (2009)
Synthesis, antimicrobial and cytotoxic activities of 1,3,4-oxadi-
azoles, 1,3,4-thiadiazoles and 1,2,4-triazoles. Eur J Med Chem
44:2106–2112
Palekar VS, Damle AJ, Shukla SR (2009) Synthesis and antibacterial
activity of some novel bis-1,2,4-triazolo[3,4-b]-1,3,4-thiadiaz-
oles and bis-4-thiazolidinone derivatives from terephthalic
dihydrazide. Eur J Med Chem 44:5112–5116
Vijesh AM, Isloor AM, Peethambar SK, Shivananda KN, Arulmoli T,
Isloor NA (2011b) Hantzsch reaction: synthesis and character-
ization of some new 1,4-dihydropyridine derivatives as potent
antimicrobial and antioxidant agents. Eur
46:5591–5597
J Med Chem
Wilson C, Gomes CRB, Vellasco WT (2008) Chemistry and
biological activities of 1,3-thiazolidin-4-ones. Mini-Rev Org
Chem 5:336–344
Porter P (2008) Westernizing women’s risks? Breast cancer in lower-
income countries. N Engl J Med 358:213–216
123