4-Aminoantipyrine-based Schiff-base transition metal complexes as potent anticonvulsant agents

Article abstract of DOI:10.1007/s00044-011-9749-3

Metal complexes of Co(II), Ni(II), Cu(II), and Zn(II) with ligands (L ¹H and L²) derived from 4-aminoantipyrine, 2-hydroxy-3-formylquinoline, and isatin were synthesized and characterized by the elemental analysis, conductance measurements, magnetic susceptibility, and spectral analysis. The spectral data revealed that the ligands acted as a neutral tridentate, coordinating to the metal ion through the azomethine nitrogen, phenolic oxygen, and carbonyl oxygen of the 4-aminoantipyrine, 2-hydroxy-3-formylquinoline, and isatin molecule in ligands L¹H and L² only. Both the ligands and their metal complexes were studied for cyclic voltammetry studies. The ligand and the metal complexes were screened for their anticonvulsant activity, and it has been observed that the metal complexes are more potent than the ligands. Springer Science+Business Media, LLC 2011.

Full text of DOI:10.1007/s00044-011-9749-3

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:2273–2279
DOI 10.1007/s00044-011-9749-3
ORIGINAL RESEARCH
4-Aminoantipyrine-based Schiff-base transition metal complexes
as potent anticonvulsant agents
•
Gurunath S. Kurdekar M. P. Sathisha
•
•
Srinivasa Budagumpi Naveen V. Kulkarni
•
•
Vidyanand K. Revankar D. K. Suresh
Received: 22 March 2010 / Accepted: 8 July 2011 / Published online: 24 July 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Metal complexes of Co(II), Ni(II), Cu(II), and
Zn(II) with ligands (L1H and L2) derived from 4-amino-
antipyrine, 2-hydroxy-3-formylquinoline, and isatin were
synthesized and characterized by the elemental analysis,
conductance measurements, magnetic susceptibility, and
spectral analysis. The spectral data revealed that the
ligands acted as a neutral tridentate, coordinating to the
metal ion through the azomethine nitrogen, phenolic oxy-
gen, and carbonyl oxygen of the 4-aminoantipyrine,
2-hydroxy-3-formylquinoline, and isatin molecule in
ligands L1H and L2 only. Both the ligands and their metal
complexes were studied for cyclic voltammetry studies.
The ligand and the metal complexes were screened for their
anticonvulsant activity, and it has been observed that the
metal complexes are more potent than the ligands.
epilepsy, the normal pattern of neuronal activity becomes
disturbed causing strange sensations, emotions and
behaviors, or sometimes convulsions, muscle spasms, and
loss of consciousness. The brain disorder in which clusters
of nerve cells or neurons in the brain sometimes signal
abnormally, which leads to the said disorders. The majority
of antiepileptic drugs have been in use since 1985. They do
not provide satisfactory seizure control in all the patients,
and typically cause notable adverse side effects (Leppik,
1994; Al-Soud et al., 2003). Research to find more effec-
tive and safer antiepileptic drugs, is, therefore, imperative
and challenging in medicinal chemistry. Antiepileptic
drugs (AEDs) are important part of the treatment program
for epilepsy, and the main aim of AEDs is to suppress them
without inducing adverse side effects. A significant rising
interest in the design of metal compounds as drugs and
diagnostic agents is currently observed in the area of sci-
entific study, appropriately termed medicinal inorganic
chemistry (Thompson and Orvig, 2006). Investigations in
this area focus mainly on the speciation of metal species in
biological media, based on possible interactions of these
metal ions with diverse biomolecules, in an effort to con-
tribute to future development of new therapeutics or
diagnostic agents (Timerbaev et al., 2006). A wide range of
metal complexes are already in clinical use and encourage
further studies for new metallodrugs, such as metal-medi-
ated antibiotics, antibacterial, antiviral, antiparasitic,
radiosensitizing agents, and anticancer compounds; among
which 4-aminoantipyrine and its complexes have been
known to possess a variety of applications in biological,
clinical, analytical, and pharmacological areas (Punniya-
murthy et al., 1995). Studies of a new kind of chemo-
therapeutic compounds are now attracting the attention of
biochemists (Choi et al., 1995; Katia et al., 1996). The
synthesized compounds were evaluated as anticonvulsant
Keywords 4-Aminoantipyrine Á Quinoline Á Isatin Á
Anticonvulsant activity Á MES
Introduction
Epilepsy, a ubiquitous disease characterized by recurrent
seizures, inflicts more than sixty million people worldwide
according to epidemiological studies (Loscher, 1998). In
G. S. Kurdekar Á M. P. Sathisha Á S. Budagumpi Á
N. V. Kulkarni Á V. K. Revankar (&)
Department of Chemistry, Karnatak University,
Pavate Nagar, Dharwad 580 003, Karnataka, India
e-mail: vkrevankar@rediffmail.com
D. K. Suresh
Department of Pharmacology, Luqman College of Pharmacy,
Gulbarga 585 102, Karnataka, India
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Med Chem Res (2012) 21:2273–2279
agents in experimental epilepsy models, i.e., maximal
electroshock test (MES) and subcutaneous pentylenetetra-
zol (sc-PTZ) induced seizure in mice. They were also
evaluated for neurotoxicity by the rotarod assay performed
in mice. In the present investigation, we have undertaken a
synthesis, characterization, and anticonvulsant evaluation
of 4-aminoantipyrine-based Schiff-base metal complexes.
Preparation of the ligands
The ligand L1H was prepared by boiling the mixture of
4-aminoantipyrine (2.03 g, 0.01 mol) and 2-hydroxy-3-
formylquinoline (1.73 g, 0.01 mol) in ethanol (40 ml). The
hot solution was allowed to cool to room temperature;
yellow solid compound was formed (Scheme 1).
The ligand L2 was prepared by the method reported
earlier (Sengupta and Gupta, 1982), and the product
formed in this case was orange-colored amorphous solid
(Scheme 1).
Experimental
All the chemicals used were of reagent grade, and the
solvents were distilled before use. Carbon, hydrogen, and
nitrogen analyses were carried out on a Thermo quest
elemental analyzer, the results of which are presented in
Table 1. The molar conductance measurements were made
on an ELICO-CM-82 conductivity bridge with a cell hav-
ing cell constant of 0.51 cm-1. The magnetic measure-
ments were obtained using Faraday balance at room
temperature using Hg[Co(SCN)6] as calibrant. Electronic
spectra of compounds in DMSO were recorded using
VARIAN CARY 50 Bio UV–visible spectrophotometer.
The IR spectra of ligands and their complexes were
recorded as KBr pellets in the region 4000–400 cm-1 on
Preparation of complexes
Ethanolic solution of metal(II) chloride {CoCl2Á6H2O
(0.237 g, 0.001 mol), NiCl2Á6H2O (0.237 g, 0.001 mol).
CuCl2Á2H2O (0.170 g, 0.001 mol) and ZnCl2 (0.136 g,
0.001 mol)} was added with stirring to an ethanolic solu-
tion of the ligand {(L1H (0.358 g, 0.001 mol), L2 (0.332 g,
0.001 mol)}, and refluxed at water bath temperature for
3–4 h. Then, the obtained complexes were filtered off,
washed with ethanol, and dried under vacuum over P2O5.
Pharmacology
1
Nicolet 170 SX FT-IR spectrometer. H NMR spectra of
ligands and zinc(II) complexes were recorded in DMSO-d6
on Bruker 300 MHz spectrometer using TMS as an internal
standard. The EPR spectra of copper(II) complexes were
recorded at room temperature on Varian E-4 X-band
spectrometer using TCNE as g-marker. The 4-aminoanti-
pyrine, and isatin were purchased from Sd-fine chemicals.
2-Hydroxy-3-formylquinoline (Meth-Cohn and Narine,
1978) is prepared by the method reported earlier.
Animals for the investigation
Wister rats of either sex weighing between 180 and 200 g
were used in the present investigation with prior permis-
sion from the Institutional Animal Ethics Committee
(IAEC). Animal studies were performed as per the rules
and regulations of CPCSEA. The animals were acclima-
tized to the experimental room having temperature
Table 1 Analytical, conductivity, and magnetic data for the ligands and their complexes
No Compounds Elemental analysis (%) found/calculated
Molar
Magnetic
moment
in leff BM
conductance
in kM mho
nbsp;cm2 mol-1
C
H
N
M
Cl
L1H (C21H18N4O2)
70.10/70.39 4.97/5.02 15.13/15.64
–
–
–
–
–
–
–
–
–
C1
C2
C3
C4
L2
[Co(C21H16N4O2)2]Á2H2O
62.01/62.15 4.14/4.43 13.16/13.81 7.02/7.26
61.98/62.17 4.15/4.44 13.19/13.81 7.11/7.22
7.8
7.4
10.1
8.2
–
5.19
[Ni(C21H16N4O2)2]Á2H2O
[Cu(C21H16N4O2)2]Á2H2O
[Zn(C21H16N4O2)2]Á2H2O
(C19H16N4O2)
3.13
61.21/61.80 4.1/4.41
61.18/61.72 3.96/4.40 13.54/13.71 7.51/7.89
68.11/68.67 4.53/4.81 16.55/16.86
13.63/13.73 7.24/7.78
1.96
Diamagnetic
–
–
C5
C6
C7
C8
[Co(C19H16N4O2)Cl2H2O]ÁH2O 45.13/45.88 3.91/4.02 11.15/11.26 11.45/11.85 13.97/14.08 13.4
[Ni(C19H16N4O2)Cl2H2O]ÁH2O 45.23/45.91 3.94/4.02 11.09/11.27 11.41/11.80 13.99/14.09 16.5
[Cu(C19H16N4O2)Cl2H2O]ÁH2O 45.09/45.46 3.89/3.98 11.07/11.16 12.31/12.66 13.67/13.95 14.8
[Zn(C19H16N4O2)Cl2H2O]ÁH2O 44.98/45.37 3.91/3.98 10.97/11.14 12.36/12.83 13.54/13.93 11.3
5.13
3.09
1.91
Diamagnetic
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Med Chem Res (2012) 21:2273–2279
2275
Scheme 1 Schematic
presentation of preparation of
ligands
H3C
H3C
NH2
O
N
N
Reflux in ethanol for 3-4 hrs
H3C
(i)
(ii)
N
H3C
N
N
H3C
N
H3C
N
HO
N
N
N
O
H
O
O
(L1H)
(L2)
(i) 2-Hydroxy-3-formylquinoline
(ii) Isatin
Testing of compounds for anticonvulsant activity
against maximal electroshock generic seizures
in Wister rats (Kulkarni, 1981)
23 2°C, controlled humidity conditions, and 12:12-h
light and dark cycle. The Wister rats were housed in sterile
Plexiglas transparent cages containing sterile paddy husk
as bedding material with maximum of four animals in each
cage. The rats were fed on autoclaved standard rat food
pellets and water ad libitum.
Previously weighed and numbered Wister rats were cat-
egorized into eight groups each consisting of four rats.
One group was used as control and the other for the
phenytoin drug treatment, and the remaining six for the
novel sample treatment. The drug phenytoin, control, and
test samples in gum acacia were administered orally to
the respective group of animals. Corneal earclip elec-
trodes were placed on the cornea of the rats, and 150 mA
of electric current was applied for 0.2 s by means of
electroconvulsiometer to all groups. Each animal was
placed into individual plexiglas transparent case and
observed for 30-min. duration (in seconds), in various
phases of convulsion, viz., tonic flexion, tonic extensor,
clonic convulsions, and stupor was noted. All the exper-
imental groups were compared with the respective control
treated with vehicle.
Acute toxicity study (Kulkarni, 1981)
For screening any synthesized compound for any of its
pharmacological properties, it is customary to carryout
acute toxicity study to determine the safe effective dose of
the synthesized compound. Wister rats of either sex
weighing between 180 and 200 g were starved for 18 h
before the experiment. The animals were divided into the
group of eight each, after recording their body weights. The
tested sample solutions of suitable concentration in 1%
gum acacia were administered orally in different groups.
Initially all the test samples were administered with
12.5 mg/kg body weight; if all the animals survived with
this dose, then the samples were tested at higher dose range
viz., 25, 50, 100, 200, and 400 mg/kg, and if the test
samples caused 100% death at this dose, the lower dose
range was treated as LD50 dose. Finally, the lethal dose
fixed for the reporting compounds is 700 mg/kg for ligands
L1H, and L2 and their complexes. The administered dose is
the one-tenth of the threshold dose.
Statistical analysis
Values are expressed as mean SEM, statistical differ-
ences between means were determined by performing one-
way ANOVA followed by Dunnett’s test. P \ 0.05 was
considered as significant difference in the present study.
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Med Chem Res (2012) 21:2273–2279
1H NMR study
Result and discussion
IR spectral study
1H NMR analysis of the ligands (L1H and L2) and their
zinc complexes (C4 and C8) were carried out in DMSO d6
solvent. Spectrum of the ligand (L1H) shows the peaks
around 10.1 and 8.8 ppm, which are ascribed to the –OH
and the azomethine protons, respectively. The signal due to
azomethine proton exhibits a downfield shift in its zinc
(C4) complex, suggesting the coordination of azomethine
nitrogen atom to the metal ion. Similarly, zinc (C4) com-
plex displays the absence of quinoline –OH proton, which
indicates the coordination of –OH group to the metal atom
via deprotonation. In the case of ligand (L2), peak
appearing at 11.1 ppm is due to the presence of the ring
(–NH) of isatin moiety. However,, the ring (–NH) of isatin
molecule retained in the spectrum of its zinc (C8) complex
is evidence for its non-involvement in the complexation.
The peak resonating around 6–8 ppm and 2–3 ppm in both
the ligands and their zinc complexes are attributed to the
aromatic proton and methyl proton, respectively.
The IR spectra providing valuable information regarding
the nature of the functional group coordinated to the metal
atom are presented in Table 2. The ligands (L1H, and L2)
showed broad bands around 1715, and 1703 cm–1,
respectively, which are attributed to the m(C=O) of anti-
pyrine molecule. A sharp band at 1680 cm–1 is assigned to
the m(C=O) of isatin system in case of ligand L2. Upon
complexation, the m(C=O) of the antipyrine molecule has
shifted to lower frequency region, suggesting that carbonyl
group is coordinated to the metal ion. The carbonyl-
stretching frequency of the isatin moiety at 1680 cm–1 has
been lowered by 60–70 cm-1 in the spectra of (C5–C8)
complexes. This clearly indicates the coordination of the
carbonyl group to the metal ion. The spectra of both the
ligands (L1H and L2) show the characteristic m([C=N)
bands in the region 1570–1500 cm-1. In the spectra of the
complexes, this band appears at lower frequency region
indicating the coordination of the azomethine nitrogen
atom to the metal ion (Guofa et al., 1990). The ligand acts
as tridentate-chelating agent coordinated to the metal ion
via the one nitrogen m([C=N) and two oxygen atoms.
Moreover, ligand L1H and L2 have shown sharp bands at
3456 and 3140 cm–1 which are the characteristic features
of the -OH and ring –NH of quinoline and isatin molecule,
respectively. Owing to the hydrated nature of the com-
plexes, it is difficult to observe the absence and the pres-
ence of the (–OH) and ring (–NH) of quinoline and isatin
molecule in all the complexes. Presence of band around
3400 cm-1 in all the complexes is the indication of coor-
dinated/lattice celled water molecule.
Molar conductivity
Molar conductivities of the complexes were measured in
DMSO solution with 10-3 M concentration. All the com-
plexes show molar conductance value in the range 7.4–16.5
mho cm2 mol-1 (Table 1). These low conductance values
suggest that the complexes are non-electrolytic in nature
(Geary, 1971).
Electronic spectra
The electronic spectra of the ligands (L1H and L2) display
the bands around 260 and 370 nm, which are assigned to
the p–p* and n–p* transitions, respectively. The n–p*
transitions are accompanied with the ([C=N–) azomethine
group of the ligands; in complexation, low shift of this
band is the indication of the coordination of azomethine
nitrogen to the metal ion. The cobalt complexes (C1 and
C5) have shown the band around 425 nm which is attrib-
uted to the LMCT. In addition to this, complex (C1) dis-
plays the band at 593 nm assigned to d–d transition. In the
same way, the nickel complexes (C2 and C6) exhibiting the
bands around 565 and 573 nm are supportive of the data
for the assigned geometry of the complexes. For the copper
(C3 and C7) and zinc (C4 and C8) complexes, bands
observed around 430–460 nm are due to the LMCT tran-
sition only.
Table 2 IR spectral data of the ligands and their complexes in cm-1
Compound
m(C=N)
(azomethine)
m(C=O)
(antipyrine)
m(C=O)
isatin
m(O–H)
L1H
C1
C2
C3
C4
L2
1596
1566
1559
1568
1560
1607
1565
1547
1560
1562
1703
1659
1640
1646
1645
1714
1691
1692
1697
1697
–
3419
3441
3448
3444
3440
–
–
–
–
–
1680
1617
1614
1619
1619
C5
C6
C7
C8
3441
3431
3432
3431
EPR spectral study
EPR studies of paramagnetic transition metal(II) com-
plexes yield information about the distribution of the
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Med Chem Res (2012) 21:2273–2279
2277
Cyclic voltammetry
unpaired electrons and, hence, about the nature of the
bonding between the metal ion and its ligands. The EPR
spectra of Cu(II) complexes (C3 and C7) were recorded at
room temperature. Complexes exhibit isotropic signal with
the g value observed to be 2.06 and 2.08, respectively, with
an absence of hyperfine splitting.
Cyclic voltammetry is a highly versatile electro-analytic
technique. In recent years, it has become as the most
popular technique for studying electrochemical reactions.
The electrochemical behaviors of ligands and their com-
plexes have been investigated in DMSO solution. Only
copper(II) complex (C7) found to be redox active in the
potential ranging from -1.0 to 1.0, with the scan rates
of 0.5, 1.0, and 1.5 V, is studied (Fig. 1). Copper com-
plex [Cu(C19H16N4O2)Cl2H2O]ÁH2O exhibit well-defined
quasireversible redox peak corresponding to the formation
of CuII ? CuIII with anodic peak at 0.320 V (Epa), fol-
lowed by the respective cathodic waves in the reverse scan
at 0.625 V (Epc) due to CuIII ? CuII reduction. The values
of Epa and Epc of the quasireversible CuII/CuIII couple
were only little affected in the scan-rate variation studies,
suggesting that there is no change in the quasireversibility.
The peak separation between Epa and Epc (DEp) found to
be greater than 59 mV supports the quasireversibility of the
redox couple, corresponding to the one-electron process.
FAB mass spectra
In the present investigation, the FAB mass spectra of both
the Cu(II) complexes (C3 and C7) have been recorded. The
molecular ion peaks observed for both the complexes are
found to be 816 and 506, respectively, which indicates that
the complexes are monomeric in nature.
Magnetic study
The experimentally determined room temperature mag-
netic susceptibilities of the complexes are presented in
Table 1. For the cobalt complexes, C1 and C5, magnetic
moment values are found to be 5.19 and 5.13 B.M
respectively, which corresponds to the presence of three
unpaired electron, and evidences the octahedral geometry
of both the complexes. The magnetic moment of the nickel
complexes, C2 and C6, are observed to be 3.13 and 3.09
B.M, respectively, which are attributed for the high-spin
configuration and show the octahedral environment around
Ni?2 ion in both the complexes. Copper complexes, C3 and
C7, have shown magnetic moment values, 1.96 and 1.91
B.M., respectively, corresponding to the presence of one
unpaired electron.
Pharmacology study
Maximal electroshock method (MES) is used as the pre-
liminary method for anticonvulsant studies of the synthe-
sized compounds, viz., L1H, L2, and (C3, C4, C7, C8) at
70 mg/kg body weight of the Wister rats. The pharmaco-
logical data of these compounds are presented in Table 3.
Information presented in Table 3 represents a thorough and
detailed presentation of test results obtained at specific
times of seizure induction in all the phases—I, II, III, and
IV of convulsion. The satisfactory anticonvulsant actions
of the above said compounds are quite long and compa-
rable to phenytoin which is used as the standard anticon-
vulsant drug, at the dose of 20 mg/kg body weight. Flexion
TG study
Thermal behaviors of (C6 and C7) complexes having
composition [Ni(C19H16N4O2)Cl2 H2O]ÁH2O and [Cu(C19
H16N4O2)Cl2 H2O]ÁH2O, respectively, have been studied
in the temperature range 40–900°C with heating rate of
10°C min-1 in a nitrogen atmosphere, where both the
complexes decompose in three steps. In the first step of
decomposition, weight loss observed in the temperature
range around 97–102°C is attributed to the loss of lattice-
celled water molecule in each case. The dehydrated
complexes (C6 and C7) continued to lose their weight in
the temperature range around 170°C, which corresponds to
the loss of one coordinated water molecule. Third step
illustrates the weight loss of ligand moiety which is
observed around temperature range 400–600°C. Above
600°C temperature, the plateau was obtained, which
indicates the formation of a respective metal oxide.
Weight losses from the TG agrees well with the theoretical
calculations.
Fig. 1 The cyclic voltammetry of the complex C7
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Med Chem Res (2012) 21:2273–2279
Table 3 Anticonvulsant activity (MES test) data of ligands, and their copper and zinc complexes
Treatment/dose mg/kg
Time (seconds) in various phases of convulsion
Flexion
Extensor
Clonus
Stupor
Control
3.16 0.28
12 0.80
19.0 3.0
5.1 4.6
20.0 0.6
4.8 6.2
3.9 7.3
20.0 0.8
4.6 4.0
4.2 5.0
220 5.0
Gum acacia 1% W/W
Phenytoin
3.10 0.5
3.19 0.4
3.03 0.4
3.01 0.6
2.6 0.4
3.05 0.8
3.0 0.2
1
0.01
170 15.5
215 7.0
156 15.0
142 12.5
205 9.0
152 8.0
145 4.0
20 mg/kg
Ligand L1H
11 0.8
5.0 0.7
7.0 0.3
11 0.5
5.5 0.4
6.5 0.7
70 mg/kg
Copper (C3) complex
70 mg/kg
Zinc (C4) complex
70 mg/kg
Ligand L2
70 mg/kg
Copper (C7) complex
70 mg/kg
Zinc (C8) complex
70 mg/kg
is the first phase of convulsion when 150 mA alternating
current was delivered for 0.2 s via corneal electrodes to the
Wister rats. At this phase, the recurrent seizures occurred in
the rats indicated by the appearance of neck jerking. The
time taken by the group of rats administered with phenyt-
oin to get recovered is 3.10 0.5, which is almost same in
the case of all the tested samples. Abolition of the hind
limb tonic extensor component indicates that the test
compound’s ability to inhibit MES-induced seizure is
observed in the extensor phase. The samples, C3, C4, C7,
and C8, have taken the shorter time period at this phase
compared with the ligands (L1H and L2). Finally, the ani-
mals were almost inactive in clonus and stupor phase, even
they cannot move. However, the animals recovered in case
of standard phenytoin drug.
Conclusion
In this research article, we have presented the syntheses of
Schiff base ligands and their later first-row transition
metal(II) complexes. The structures of the ligands and their
metal complexes were confirmed by various spectral and
elemental analyses. The ligand-to-metal (L:M) stoichiom-
etry is found to be 2:1 and 1:1 in case of L1H and L2,
respectively (Fig. 2). The present study suggests the
coordination of the ligands to the metal ions in N, O, O
fashion. All the complexes are found to be non-electrolytic
in nature with octahedral geometry. The prepared com-
pounds were evaluated for pharmacological properties and
have exhibited promising anticonvulsant activity toward
the electroshock-induced seizures in Wistar rats. The
Fig. 2 The tentative structure
of the complexes
H3C
N
N
H3C
O
N
N
O
H3C
NH
N
N
.2H2O
Cl
.
N
H2O
O
M
O
H2O
H3C
O
M
Cl
O
N
N
N
CH3
N
CH3
M= Co(II), Ni(II), Cu(II) and Zn(II)
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Med Chem Res (2012) 21:2273–2279
2279
Katia B, Simon L, Anne R, Gerard C, Francoise D, Bernard M (1996)
Synthesis and characterization of chiral Schiff base complexes
with diiminobinapthyl or diiminocyclohexyl moieties as poten-
tial enantioselective epoxidation catalysts. Inorg Chem 35:387
Kulkarni SK (1981) Actions of clonidine on convulsions and
behavior. Arch Int Pharmacodyn 252:124
Leppik IE (1994) Antiepileptic drugs in development: prospects for
the near future. Epilepsia 35:29
Loscher W (1998) New visions in the pharmacology of anticonvul-
sion. Eur J Pharmacol 1:342
complexes have shown better activity as compared to their
ligands.
Acknowledgments The authors thank the Department of Chemistry
and USIC, the Karnatak University, Dharwad for providing research
and spectral facilities. Facilities provided for recordings of FAB mass
spectra (by the CDRI, Lucknow) and EPR spectra (by the IIT Bom-
bay) are gratefully acknowledged. Further, the authors thank the UGC
and the Karnatak University for providing research fellowships.
Meth-Cohn O, Narine B (1978) A versatile new synthesis of
quinolines, thienopyridines and related fused pyridines. Tetra-
hedron Lett 19:2045–2048
References
Punniyamurthy T, Kalra SJS, Iqbal J (1995) Cobalt(II) catalyzed
biomimetic oxidation of hydrocarbons in the presence of
dioxygen and 2-methylpropanal. Tetrahedron Lett 36:8497
Sengupta AK, Gupta AA (1982) Synthesis of some 4-(1,5-
disubstituted-2-oxoindolinyldeneimino)-2,3-dimethyl-1-phenyl-
D3-pyrazoline-5-ones as possible pesticides. Ind J Chem 21B:72
Thompson KH, Orvig C (2006) Metal complexes in medicinal
chemistry: new vistas and challenges in drug design. J Chem Soc
Dalton Trans 6:761
Timerbaev AR, Hartinger CG, Aleksenko SS, Keppler BK (2006)
Interactions of antitumor metallodrugs with serum proteins:
Advances in characterization using modern analytical method-
ology. Chem Rev 106:2224
Al-Soud YA, Al-Masoudi NA, Ferwanah Ael R (2003) Synthesis and
properties of new substituted 1,2,4-triazoles: potential antitumor
agents. Bioorg Med Chem 11:1701
Choi YK, Chjo KH, Park SM, Doddapaneni N (1995) Oxygen
reduction at Co(II)2-disalophen modified carbon electrodes.
J Electrochem Soc 142:4107
Geary WJ (1971) The use of conductivity measurements in organic
solvents for the characterisation of coordination compounds.
Coord Chem Rev 7:81
Guofa L, Chowngwu N, Bin L, Kunyuan M (1990) Complexes of
lanthanide nitrates with a Schiff base derived from o-vanillin and
p-toluidine. Polyhedron 9:2019
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