New palladium(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones: Synthesis, spectral studies and in vitro anti-amoebic activity

Article abstract of DOI:10.1016/S0968-0896(03)00213-X

Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type [Pd(TSCN)Cl₂] (where TSCN=thiosemicarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)₂Cl₂], respectively. Coordinati

Full text of DOI:10.1016/S0968-0896(03)00213-X

Bioorganic & Medicinal Chemistry 11 (2003) 2923–2929
New Palladium(II) Complexes of 5-Nitrothiophene-2-
carboxaldehyde Thiosemicarbazones:
Synthesis, Spectral Studies and In Vitro Anti-Amoebic Activity
Neelam Bharti,y Shailendra, Sangita Sharma, Fehmida Naqvi and Amir Azam*
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
Received 11 November 2002; accepted 24 March 2003
Abstract—Thiosemicarbazones (1–7) and their palladium(II) complexes (1a–7a) of the type [Pd(TSCN)Cl2] (where TSCN=thiose-
micarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)2Cl2], respectively. Coordination via the
thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to the metal ion were confirmed by spectral data.
These compounds were screened in vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal properties. Enhance-
ment of antiamoebic activity resulted due to the introduction of palladium metal in the thiosemicarbazone moiety. The most
promising of the group tested are [Pd(5-N-2-TCA-COTSCN)Cl2] and [Pd(5-N-2-TCA-AdmTSCN)Cl2] comparable to that of
metronidazole.
# 2003 Elsevier Science Ltd. All rights reserved.
Introduction
ability to form chelates with heavy metals.13À15 Biologi-
cal activities of metal complexes differ from those of
either ligands or the metal ions and increased and/or
decreased biological activities are reported for several
transition metal complexes, such as copper(II) and
nickel(II).10À12 Thiosemicarbazones are versatile com-
pounds: structural isomers (E, E0, Z) are reported15 and
they coordinate to the metal either as a neutral ligand or
as a deprotonated ligand through the S, N, N atoms or
through the O, N, S atoms.16 Thiosemicarbazones con-
taining a pyridine ring give rise to NNS tridentate sys-
tems have been extensively investigated due to their
biological properties.17,18 However, thiosemicarbazones
with non-pyridine heterocyclic rings have not been
exhaustively studied.19À21
Entamoeba histolytica, the causative agent for human
amoebiasis, is an enteric protozoan parasite capable of
invading the mucosa of the colon and entering the
blood circulation to reach various extraintestinal
organs.1 Fifty million people suffer from amoeba
induced colitis or extra intestinal abscesses resulting in
100,000 deaths annually.2 The nitroimidazoles are the
principal drugs of choice in the treatment of amoebiasis
since they are effective against extra intestinal and
intestinal wall infection. Metronidazole, the leading
drug, has been shown to be both mutagenic and carci-
nogenic in animals.3,4 A new amoebicide with at least
equivalent efficacy to metronidazole, well tolerated, with
no carcinogenic potential, would provide a new dimension
in therapy.
Uses of metal ions in therapeutic agents are known to
accelerate drug action and their efficacy enhanced upon
the coordination with a metal ion.22,23 The classical
coordination complex, cis-DDP or cisplatin (cis-dia-
mmine dichloroplatinum),24 has been the subject of
much recent attention towards the metal-based chemo-
therapy, because of its beneficial effects in the treatment
of cancer.25,26 The significant anti-trypanosomal activ-
ity27 of semicarbazones of 5-nitrothiophene-2-carbox-
aldehyde led us to study the screening of
thiosemicarbazones and their palladium(II) complexes
as antiamoebic agents. Continuing our efforts to
Thiosemicarbazones are of considerable interest because
of their chemistry and potentially beneficial biological
activities, such as antitumor, antibacterial, antiviral and
antimalarial activities.5À12 The biological activities of
thiosemicarbazones are considered to be due to their
*Corresponding author. Tel.: +91-11-6831717/338; fax: +91-11-
6821232/0229; e-mail: amir_sumbul@yahoo.co.in
yPresent address: Department of Medicinal Chemistry, University of
Florida, Gainesville, FL 32610, USA.
0968-0896/03/$ - see front matter # 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0968-0896(03)00213-X

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N. Bharti et al. / Bioorg. Med. Chem. 11 (2003) 2923–2929
develop improved antiamoebic drugs, we have recently
reported Pd(II) and Ru(II) complexes of NS donor
ligands, which showed promising activity against
E. histolytica.28À30
with the free ligand along with their thermo gravimetric
analysis.
IR and electronic spectral studies of the complexes
The present work deals with the synthesis of new thiose-
micarbazones (Fig. 1) and their Pd(II) complexes (Fig. 2).
The structures of all the compounds were elucidated by
The thiosemicarbazones 1–7 can exist thione and thiol
tautomeric form Ia and Ib, respectively.
1
IR, UV, H NMR and elemental analysis. These com-
pounds were tested in vitro against HK-9 strain of E.
histolytica for their ability to inhibit the growth of
parasite, resulted that the chelation induce significant
changes in the antiamoebic activity.
However, the existence of a strong band in the region
1028–1082 cmÀ1 due to n(C¼S) and absence of any
band in the region 2500–2600 cmÀ1 due to n(C–SH)
suggesting that all the thiosemicarbazones remain in
Results and Discussion
Reaction of 5-nitrothiophene-2-carboxaldehyde thiose-
micarbazones with [Pd(DMSO)2Cl2] gave amorphous
solid compounds. All the compounds were isolated in
good yield and are stable both in the solid and solution
state. Analytical data of these compounds are in good
agreement with their composition (Table 1). The com-
plexes are insoluble in water, methanol and ethanol,
soluble in DMF and DMSO. The complexes do not
undergo any weight loss up to 240 ꢀC, which suggest
their fair thermal stability. The structure of the com-
plexes presented in Figure 2 was established by com-
paring spectral data (IR, UV–visible and 1H NM R)
Figure 2. Structure of palladium(II) complexes: (1a) R= –NHC7H7;
(2a) R= –NHC7H7; (3a) R= –NHC7H7; (4a) R= –NC5H12; (5a) R=
–NC8H10; (6a) R= –NHC8H15; (7a) R= –NHC10H15).
Figure 1. 1. 5-N-2-TCA-o-TolTSCN, 5-nitrothiophene-2-carboxaldehyde-o-toludinethiosemicarbazone; 2. 5-N-2-TCA-m-TolTSCN, 5-nitrothio-
phene-2-carboxaldehyde-m-toludinethiosemicarbazone; 3. 5-N-2-TCA-p-TolTSCN, 5-nitrothiophene-2-carboxaldehyde-p-toludinethiosemicarbazone;
4. 5-N-2-TCA-NMBuTSCN, 5-nitrothiophene-2-carboxaldehyde-n-methylbutylthiosemicarbazone; 5. 5-N-2-TCA-NMBzTSCN, 5-nitrothiophene-2-
carboxaldehyde-n-methylbenzylthiosemicarbazone; 6. 5-N-2-TCA-COTSCN, 5-nitrothiophene-2-carboxaldehyde-cyclooctylthiosemicarbazone; 7. 5-N-
2-TCA-AdmTSCN, 5-nitrothiophene-2-carboxaldehyde-admantaminethiosemicarbazone.

N. Bharti et al. / Bioorg. Med. Chem. 11 (2003) 2923–2929
2925
Table 1. Analytical and physicochemical data of thiosemicarbazones and their new palladium(II) complexes
S. no.
Compd/stoichiometrya
Colour
Yield (%)
Mp/Dec. temp (ꢀC)
Found (calcd)
C
H
N
Cl
1.
5-N-2-TCA-o-TolTSCN
C13H12N4S2O2
[Pd(5-N-2-TCA-o-TolTSCN)Cl2]
C13H12N4S2O2Cl2Pd
5-N-2-TCA-m-TolTSCN
C13H12N4S2O2
[Pd(5-N-2-TCA-m-TolTSCN)Cl2]
C13H12N4S2O2Cl2Pd
5-N-2-TCA-p-TolTSCN
C13H12N4S2O2
[Pd(5-N-2-TCA-p-TolTSCN)Cl2]
C13H12N4S2O2Cl2Pd
5-N-2-TCA-NMBuTSCN
C11H16N4S2O2
[Pd(5-N-2-TCA-NMBuTSCN)Cl2]
C11H16N4S2O2Cl2Pd
5-N-2-TCA-NMBzTSCN
C14H14N4S2O2
[Pd(5-N-2-TCA-NMBzTSCN)Cl2]
C14H14N4S2O2Cl2Pd
5-N-2-TCA-COTSCN
C14H20N4S2O2
[Pd(5-N-2-TCA-COTSCN)Cl2]
C14H20N4S2O2Cl2Pd
5-N-2-TCA-AdmTSCN
C16H24N4S2O2
[Pd(5-N-2-TCA-AdmTSCN)Cl2]
C16H24N4S2O2Cl2Pd
Yellow
Brick red
49
51
53
43
51
47
72
67
87
56
52
63
67
73
180
197
195
205
200
207
188
222
184
235
183
214
154
218
48.92
(48.75)
31.10
(31.45)
48.90
(48.75)
31.15
(31.45)
48.91
(48.75)
31.29
(31.45)
44.34
(44.00)
27.34
(27.73)
50.05
(50.30)
32.72
(32.94)
49.57
(49.41)
32.40
(32.56)
51.85
3.56
(3.75)
2.56
(2.42)
3.58
(3.75)
2.54
(2.42)
3.60
(3.75)
2.56
(2.42)
5.39
(5.33)
3.49
(3.36)
4.40
(4.19)
2.40
(2.74)
6.01
(5.88)
3.54
(3.88)
6.89
17.43
(17.50)
11.43
(11.29)
17.47
(17.50)
11.56
(11.29)
17.53
(17.50)
11.43
(11.29)
18.92
(18.67)
11.92
(11.74)
16.44
(16.77)
11.24
(10.98)
16.24
(16.47)
10.41
(10.85)
15.50
1a
2.
14.20
(14.31)
Reddish yellow
Brick red
2a
3.
14.59
(14.31)
Yellow
3a.
4.
Brick red
14.20
(14.31)
Dark brown
Brick red
4a.
5.
14.67
(14.92)
Red
5a.
6.
Brick red
14.04
(13.92)
Light yellow
Brick red
6a.
7.
13.59
(13.76)
Brownish yellow
Brick red
(52.17)
35.64
(35.55)
(6.52)
3.56
(3.70)
(15.22)
10.43
(10.37)
7a.
13.40
(13.15)
aFor abbreviations, see Figure 1.
their thione form. The band due to n(C–S–C) (ring) of
thiophene moiety remains unaltered thereby indicating
the non-involvement of ring sulphur in coordination.
The negative shift (14–39 cmÀ1) of n(C¼N) band
observed in all complexes indicates the involvement of
azomethine nitrogen upon complexation.31 This was
further supported by the upward shift of N–N band of
ligand on coordination. The strong band at 1028–1082
cmÀ1 ascribed to n(C¼S) of ligands is shifted to lower
frequency (13–35 cmÀ1) indicating the bonding of metal
through thionic sulphur. The broad band observed in
region 3159–3251 cmÀ1 due to n(N–H) stretch is only
slightly affected on the coordination. The preferential
coordination of thionic sulphur over sulphur of thio-
phene is due to more nucleophilic character of the former.
noticed earlier in other palladium(II) complexes of
similar ligands systems.32,33
1H NMR spectral analysis
Further evidence for the coordinating mode of the
1
thiosemicarbazones 1–7 was obtained from H NM R
spectra. The 1H NMR spectra of thiosemicarbazones 1–
7 recorded in DMSO-d6 exhibit a broad peak at 9.82–
10.98 ppm due to –NH proton, which indicate that even
in a polar solvent they remain in the thione form. The –
NH proton signal of the thiosemicarbazones usually
shifts to up field and appear at 3.32–3.71 ppm in their
respective complexes. In complexes 4a and 6a, we are
unable to locate –NH proton signal. This either merges
with aromatic protons or resonates beyond 15 ppm.
This information suggests the adjustment of electronic
current upon coordination of >C¼S group to the metal
ion. Other protons, namely viz. CH3 protons, CH2 pro-
tons and aryl carbons in complexes 1a–7a resonate
nearly at the same region as that of free ligands.
The electronic spectra of the ligands exhibit three bands
in the region 24,691–25,752, 35,461–37,879 and 47,846–
48,780 cmÀ1. The probable assignment for these bands
are due to the n!p*, p!p* and j!j* transitions,
respectively. In the spectra of complexes, these bands
appeared at ca. 21,500, 37,000 and 49,500 cmÀ1 respec-
tively with little change in the energy of these bands.
The band appeared at ca. 37,000 and 49,500 cmÀ1 are
assigned to p!p* and j!j* transitions, respectively.
As intensity of the band appearing at ca. 21500 cmÀ1 is
comparable with other ligand bands, this is assigned due
to n!p* transition. The band due to ligand to metal
charge transfer transition is probably appearing under-
neath to n!p* transition and is usually not seen in the
present complexes. Such observations have also been
TGA analysis
The TGA (under nitrogen, rate 10 ꢀ/min) profiles of
complexes along with the % weight at different tem-
peratures were recorded. These complexes do not lose
weight up to 245 ꢀC. Further increment of temperature
causes decomposition of the complexes in two steps. The
temperature range for the first step being 245–395 ꢀC
where loss of mixed fragments was observed. The second

2926
N. Bharti et al. / Bioorg. Med. Chem. 11 (2003) 2923–2929
step starts immediately after first one and continues
until the complete decomposition of the ligand and for-
mation of MS [M=Pd(II)] as the end product. The
total% weight loss corresponds to the loss of the
respective ligand after considering the transfer of one
sulphur atom to the metal ion and residue
corresponds to the metal sulphide.
transition metal complexes of NS donor ligands showed
good anti-amoebic activity against the same strain of E.
histolytica.28À30 It was noted that antiparasitic activity was
limited to those compounds in which the alkylidene group
is attached to the 2-position, rather than 3- or 4-position
of the heterocyclic ring and also to those in which a thio-
carbonyl, rather than a carbonyl group, is present.36
The importance of such work lies in the possibility that
the new complexes might be more efficacious drugs
against amoebiasis for which a thorough investigation
regarding the structure–activity of the complexes and
their stability is required in order to understand the
variation in their biological effects, which could be
helpful in designing more potent anti-amoebic agents
therapeutic use.
Biological activity
All the compounds were evaluated for anti-amoebic
activity in vitro using HK-9 strain of E. histolytica. The
IC50 values in micro molar are shown in Table 2. The
free ligands 1–7 exhibited anti-amoebic activity with
IC50 of 1.73–7.70 m M. Considering the substitutions at
N4 position in thiosemicarbazones with cyclooctyl
amine (6) and adamantamine (7) turned out to be
potent anti-amoebic agents (IC50=1.71–1.73 mM ) as
compared to standard anti-amoebic drug, metroni-
dazole (IC50=2.05 mM). Complexation of the thiosemi-
carbazones with Pd(II) results in compounds (1a–7a),
which showed a significant improvement in anti-amoe-
bic activity towards HK-9 strain of E. histolytica
(IC50=0.73–4.06 mM). All the complexes are more
active than their respective ligands indicate that the
complexation to metal enhances the activity of the
ligand. This may be explained by Tweedy’s theory,34
according to which chelation reduces the polarity of the
central metal atom because of partial sharing of its
positive charge with the ligand, which favors permea-
tion of the complexes through the lipid layer of cell
membrane. The most active compounds in this class
were again those thiosemicarbazone Pd(II) complexes,
which have cyclooctyl amine (6a, IC50=0.81 m M) and
Conclusion
Although the synthesis of thiosemicarbazones and their
metal complexes were reported several years ago, very
little is known about their anti-amoebic activity. This
research examined the biological activities of the new
thiosemicarbazones prepared from 5-nitrothiophene-2-
carboxaldehyde and their Pd(II) complexes. The sub-
stituents did not have any influence on the coordination
and chelation of compounds that showed the same SN
bidentate behavior. HK-9 strain of E. histolytica was
employed for in vitro anti-amoebic evaluation. The
biological behavior revealed that most of the ligands
show a weak activity against E. histolytica. The chela-
tion induced significant changes in the biological activ-
ity of the ligands and the palladium complexes 6a and
7a have shown greater activity, whereas complexes 1a–
3a and 5a showed similar activity as metronidazole in
vitro.
4
adamantamine (7a, IC50=0.73 m M ) as N substitution.
It is concluded that the presence of these bulky groups
at position N4 of the thiosemicarbazone moiety
enhanced anti-amoebic activity. It has also been
observed by the other researchers.35 The Pd-complex
precursor [Pd(DMSO)2Cl2] was also evaluated for anti-
amoebic activity and compared with Pd(II) complexes
and metronidazole, which showed no activity against E.
histolytica. In our earlier studies, it was found that the
Experimental
Materials and methods
Palladium chloride was purchased from Aldrich chemi-
cal
company
(USA).
All
the
Cycloalkyl-
prepared as
Table 2. In vitro anti-amoebic activities of thiosemicarbazones and
their Pd(II) complexes against (HK-9) strain of E. histolytica
aminothiocarbonylhydrazines
were
reported earlier.37 The metal precursor [Pd(DMSO)2Cl2]
was prepared by the literature method.38 Elemental
analysis (C, H, N) was carried out by Central Drug
Research Institute, Lucknow, India. Chlorine was esti-
mated by standard method. Melting points were recor-
ded on a KSW melting point apparatus and were
uncorrected. Electronic spectra were recorded in DMF
on a Shimadzu UV-1601 PC UV-Visible spectro-photo-
meter. IR spectra on KBr disks were recorded on a
Perkin-Elmer model 1620 FT-IR spectrophotometer. 1H
NMR spectra were obtained at ambient temperature
using a Bruker spectrospin DPX-300 MHz spectro-
photometer in CDCl3 and DMSO-d6 using tetra-
methylsilane as an internal standard. Thermograms of
the complexes were recorded under nitrogen on a TG 51
thermo gravimetric analyzer with increasing the
temperature at 10 ꢀC per minute.
a
S. no.
Compd
IC50 (mM
)
SD
1.
1a.
2.
2a.
3.
3a.
4.
4a.
5.
5a.
6.
6a.
7.
7a.
5-N-2-TCA-o-TolTSCN
[Pd(5-N-2-TCA-o-TolTSCN)Cl2]
5-N-2-TCA-m-TolTSCN
[Pd(5-N-2-TCA-m-TolTSCN)Cl2]
5-N-2-TCA-p-TolTSCN
[Pd(5-N-2-TCA-p-TolTSCN)Cl2]
5-N-2-TCA-NMBuTSCN
[Pd(5-N-2-TCA-NMBuTSCN)Cl2]
5-N-2-TCA-NMBzTSCN
[Pd(5-N-2-TCA-NMBzTSCN)Cl2]
5-N-2-TCA-COTSCN
[Pd(5-N-2-TCA-COTSCN)Cl2]
5-N-2-TCA-AdmTSCN
[Pd(5-N-2-TCA-AdmTSCN)Cl2]
[Pd(DMSO)2Cl2]
Metronidazole
4.59
1.95
4.78
2.05
4.65
1.99
7.70
4.06
3.71
1.70
1.73
0.81
1.71
0.73
8.15
2.05
0.87
0.26
0.74
0.33
0.82
0.35
1.69
1.78
0.54
0.36
0.37
0.22
0.41
0.18
1.73
0.33
aSD, standard deviation.

N. Bharti et al. / Bioorg. Med. Chem. 11 (2003) 2923–2929
2927
Synthesis of 5-nitrothiophene-2-carboxaldehyde thiosemi-
carbazones
methanol. The solution was kept at 0 ꢀC overnight, the
product was separated by filtration and finally washed
with methanol. Recrystallization was effected in metha-
nol/DMF (8:2).
All thiosemicarbazones were synthesized by mixing an
aqueous solution of cycloalkylaminothiocarbonyl-
hydrazines (0.003 mol in 10 mL) and ethanolic solution
of 5-nitrothiophene-2-carboxaldehyde (0.003 mol in 10
mL) at 25 ꢀC for 3 h with continuous stirring. After
cooling, the precipitated compound was filtered and
recrystallized from appropriate solvent.
Â
Ã
CH3OH
PdðDMSOÞ2Cl2 þ TSCN ÀÀÀ! ½PdðTSCNÞCl2ꢀ
5 h; reflux
þ 2 DMSO
5-N-2-TCA-o-TolTSCN (1). Yellow solid (methanol);
max/cmÀ1: 25,752, 35,722, 48,490; IR: nmax/cmÀ1: 3236
(where TSCN=thiosemicarbazones 1–7).
l
(NH), 1587 (C¼N), 1502 (C¼C), 1113 (C–N), 1035 (C¼S);
1H NM R ((CD) SO)/ppm: 8.42 (1H, s, –CH¼N), 10.61
3 2
(2H, s, –NH), 1.98 (3H, s, –CH3), 7.20–8.04 (6H, m, aryl).
[Pd(5-N-2-TCA-oTolTSCN)Cl2] (1a). Brick red solid;
l
max/cmÀ1: 21,453, 36,418, 49,513; IR: nmax/cmÀ1: 3435
5-N-2-TCA-m-TolTSCN (2). Reddish yellow solid
(methanol); lmax/cmÀ1: 24,752, 35,842, 48,780; IR: nmax
(NH), 1563 (C¼N), 1500 (C¼C), 1018 (C¼S), 495, 428
(MÀN, MÀS); 1H NMR ((CD3)2SO)/ppm.: 7.96 (1H, s,
–CH¼N), 3.68 (1H, s, –NH), 10.38 (1H, s, –NH), 2.03
(3H, s, –CH3), 7.23–8.09 (6H, m, Aryl).
/
cmÀ1: 3217 (NH), 1600 (C¼N), 1504 (C¼C), 1143 (C–
1
N), 1034 (C¼S); H NMR ((CD3)2SO)/ppm: 8.04 (1H,
s, –CH¼N), 9.87 (2H, s, –NH), 2.53 (3H, s, –CH3),
7.03–8.42 (6H, m, aryl).
[Pd(5-N-2-TCA-mTolTSCN)Cl2] (2a). Brick red solid;
max/cmÀ1: 21,945, 36,315, 49,419; IR: nmax/cmÀ1: 3437
l
5-N-2-TCA-p-TolTSCN (3). Yellow solid (methanol);
l
(NH), 1599 (C¼N), 1531 (C¼C), 1142 (C–N), 1035
(C¼S); 1H NMR ((CD3)2SO)/ppm: 8.36 (1H, s,
–CH¼N), 9.82 (2H, s, –NH), 2.40 (3H, s, –CH3), 6.98–
7.85 (6H, m, aryl).
(NH), 1582 (C¼N), 1499 (C¼C), 1012 (C¼S), 498, 441
1
max/cmÀ1: 24,938, 37,879, 48,309; IR: nmax/cmÀ1: 3239
(MÀN, MÀS); H NMR ((CD3)2SO)/ppm: 7.34 (1H, s,
–CH¼N), 3.71 (1H, s, –NH), 9.96 (1H, s, –NH), 2.06
(3H, s, –CH3), 7.20–8.02 (6H, m, Aryl).
[Pd(5-N-2-TCA-p-TolTSCN)Cl2] (3a). Brick red solid;
max/cmÀ1: 22,340, 38,112, 49,415; IR: nmax/cmÀ1: 3435
l
5-N-2-TCA-NMBuTSCN (4). Dark brown solid (ace-
tone); lmax/cmÀ1: 24,846, 37,879, 48,537; IR: nmax/cmÀ1
(NH), 1585 (C¼N), 1529 (C¼C), 1022 (C¼S), 517, 429
1
:
(MÀN, MÀS); H NMR ((CD3)2SO)/ppm: 7.72 (1H, s,
3221 (NH), 1525 (C¼N), 1487 (C¼C), 1123 (C–N), 1047
–CH¼N), 3.69 (1H, s, –NH), 9.68 (1H, s, –NH), 2.05
(C¼S); 1H NM R ((CD) SO)/ppm: 8.37 (1H, s, CH¼N),
(3H, s, –CH3), 7.18–8.03 (6H, m, Aryl).
3 2
10.98 (1H, s, –NH), 4.43 (6H, m, –CH2), 2.69 (3H, s,
–CH3), 2.47 (3H, t, –CH3), 7.09–7.94 (2H, m, aryl).
[Pd(5-N-2-TCA-NMBuTSCN)Cl2] (4a). Brick red solid;
max/cmÀ1: 22,010, 38,011, 49,229; IR: nmax/cmÀ1: 3446
l
5-N-2-TCA-NMBzTSCN (5). Red solid (chloroform);
(NH), 1510 (C¼N), 1485 (C¼C), 1012 (C¼S), 510, 435
1
l
max/cmÀ1: 24,938, 37,313, 47,846; IR: nmax/cmÀ1: 3186
(MÀN, MÀS); H NMR ((CD3)2SO)/ppm: 7.86 (1H,
(NH), 1524 (C¼N), 1493 (C¼C), 1105 (C–N), 1028
(C¼S); 1H NMR ((CD3)2SO)/ppm: 8.46 (1H, s,
–CH¼N), 10.79 (1H, s, –NH), 4.63 (2H, s, –CH2), 2.89
(3H, s, –CH3), 7.21–8.06 (7H, m, aryl).
s, –CH¼N), 2.41 (3H, s, –CH3), 2.23 (3H, m, –CH3),
4.41 (6H, m, –CH2), 7.13–7.99 (2H, m, Aryl).
[Pd(5-N-2-TCA-NMBzTSCN)Cl2] (5a). Brick red solid;
max/cmÀ1: 21,445, 36,454, 49,750; IR: nmax/ cmÀ1: 3491
l
5-N-2-TCA-COTSCN (6). Light yellow solid (metha-
nol); lmax/cmÀ1: 24,691, 35,461, 48,020; IR: nmax/cmÀ1
(NH), 1505 (C¼N), 1487 (C¼C), 1007 (C¼S), 490, 423
1
:
(MÀN, MÀS); H NMR ((CD3)2SO)/ppm: 8.07 (1H, s,
3159 (NH), 1580 (C¼N), 1525 (C¼C), 1136 (C–N),
–CH¼N), 3.32 (1H, s, –NH), 2.92 (3H, s, –CH3), 4.69
1
1082 (C¼S); H NMR ((CD3)2SO)/ppm: 8.33 (1H, s,
(2H, s, –CH2), 7.16–8.01 (7H, m, Aryl).
–CH¼N), 9.87 (1H, s, –NH), 8.19 (1H, d, –NH), 4.45
(14H, m, –CH2), 7.02–7.67 (2H, m, aryl).
[Pd(5-N-2-TCA-COTSCN)Cl2] (6a). Brick red solid;
max/cmÀ1: 21670, 37109, 49654; IR: nmax/cmÀ1: 3460
l
5-N-2-TCA-AdmTSCN (7). Brownish yellow solid
(N–H), 1541 (C¼N), 1516 (C¼C), 1054 (C¼S), 502, 453
1
(methanol); lmax/cmÀ1: 24,938, 37,879, 48,309; IR: nmax
/
(MÀN, MÀS); H NMR ((CD3)2SO)/ppm: 7.78 (1H,
cmÀ1: 3251 (NH), 1584 (C¼N), 1518 (C¼C), 1132
(C–N), 1074 (C¼S); 1H NMR ((CD3)2SO)/ppm: 8.29
(1H, s, –CH¼N), 10.04 (1H, s, –NH), 8.45 (1H,
d, –NH), 4.53 (18H, m, –CH2), 7.21–8.03 (2H, m, aryl).
s, –CH¼N), 8.07 (1H, d, –NH), 4.48 (14H, m, –CH2),
6.97–7.69 (2H, m, Aryl).
[Pd(5-N-2-TCA-AdmTSCN)Cl2] (7a). Brick red solid;
l
max/cmÀ1: 21,431, 37,552, 49,112; IR: nmax/cmÀ1: 3435
(NH), 1565 (C¼N), 1504 (C¼C), 1052 (C¼S), 516, 458
(M–N, M–S); 1H NMR ((CD3)2SO)/ppm: 7.65 (1H,
s, –CH¼N), 3.42 (1H, s, –NH), 8.39 (1H, d, –NH), 4.32
(18H, m, –CH2), 7.17–8.09 (2H, m, Aryl).
Preparation of palladium(II) complexes
All Pd(II) complexes were prepared by mixing the equi-
molar ratio of ligand and [Pd(DMSO)2Cl2] in refluxing

2928
N. Bharti et al. / Bioorg. Med. Chem. 11 (2003) 2923–2929
In vitro testing against E. histolytica
References and Notes
The thiosemicarbazones and their Pd(II) complexes
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inhibition of amoeba occurs41,42 and the stock solutions
of the compounds were prepared freshly before use at a
concentration of 1 mg/mL. Two-fold serial dilutions
were made in the wells of 96-well microtiter plate
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This work was supported from Council of Scientific and
Industrial Research [Grant no. 27(0117)/02/EMR-ll],
New Delhi, India. Shailendra acknowledges the senior
research fellowship from CSIR, New Delhi, India. The
authors are thankful to Prof. Alok Bhattacharya and
Dr. Sudha Bhattacharya, School of Life Sciences and
School of Environmental Sciences, Jawaharlal Nehru
University, New Delhi, respectively, for providing
Laboratory facilities for biological activities.

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