Menthone aryl acid hydrazones: A new class of anticonvulsants

Article abstract of DOI:10.2174/157340611794072689

A series of ten compounds (Compounds J₁-J₁₀) of (±) 3-menthone aryl acid hydrazone was synthesized and characterized by thin layer chromatography and spectral analysis. Synthesized compounds were evaluated for anticonvulsant activity after intraperitoneal (i.p) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure method and minimal clonic seizure test. Minimal motor impairment was also determined for these compounds. Results obtained showed that four compounds out of ten afforded significant protection in the minimal clonic seizure screen at 6 Hz. Compound J₆, 4-Chloro-N-(2-isopropyl-5- methylcyclohexylidene) benzohydrazide was found to be the most active compound with MES ED₅₀ of 16.1 mg/kg and protective index (pI) of greater than 20, indicating that (±) 3-menthone aryl acid hydrazone possesses better and safer anticonvulsant properties than other reported menthone derivatives viz. menthone Schiff bases, menthone semicarbazides and thiosemicarbazides.

Full text of DOI:10.2174/157340611794072689

56
Medicinal Chemistry, 2011, 7, 56-61
Menthone Aryl Acid Hydrazones: A New Class of Anticonvulsants
Jainendra Jain1,*, Y. Kumar2, Reema Sinha1, Rajeev Kumar1 and James Stables3
1Department of Pharmacy, RamEesh Institute of Vocational and Technical Education, 3, Knowledge Park I, Greater
Noida, GautamBudh Nagar, Uttar Pradesh-201308, India
2ITS Paramedical College (Pharmacy), Muradnagar, Ghaziabad, Uttar Pradesh-201206, India
3National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Health, Bethesda, MD 20892-
9020, USA
Abstract: A series of ten compounds (Compounds J1–J10) of (±) 3-menthone aryl acid hydrazone was synthesized and
characterized by thin layer chromatography and spectral analysis. Synthesized compounds were evaluated for anticonvul-
sant activity after intraperitoneal (i.p) administration to mice by maximal electroshock (MES) and subcutaneous pentyle-
netetrazole (scPTZ) induced seizure method and minimal clonic seizure test. Minimal motor impairment was also deter-
mined for these compounds. Results obtained showed that four compounds out of ten afforded significant protection in the
minimal clonic seizure screen at 6 Hz. Compound J6, 4-Chloro-N-(2-isopropyl-5-methylcyclohexylidene) benzohydrazide
was found to be the most active compound with MES ED50 of 16.1 mg/kg and protective index (pI) of greater than 20, in-
dicating that (±) 3-menthone aryl acid hydrazone possesses better and safer anticonvulsant properties than other reported
menthone derivatives viz. menthone Schiff bases, menthone semicarbazides and thiosemicarbazides.
Keywords: (±) 3-menthone, aryl acid hydrazone, anticonvulsant, MES, scPTZ, minimal clonic seizure, protective index (pI).
1. INTRODUCTION
to interact with a macromolecular complex in vivo as dis-
cussed in previous paper [6, 7]. Aryl semicarbazones contain
large hydrophobic group in close proximity to two electron
donor atoms, thus fulfilling the criterion of structural re-
quirements for MES test [8].
Epilepsy is a neurological disorder of varied etiology. It
is characterized by paroxysmal, excessive and hyper syn-
chronous discharges of large number of neurons [1]. Ap-
proximately 50 million people worldwide suffer from epi-
lepsy, making this condition, the second leading neurological
disorder. Today there is a need for new antiepileptic drugs
since approximately one quarter of epileptic patients finds
that present drug therapy inadequately controls their convul-
sions [2]. In addition, many currently used antiepileptic
drugs cause significant side effects which may limit their
maximal usefulness [3]. In recent years, the field of antiepi-
leptic drug development (AED) has become quite dynamic,
affording many promising research opportunities. Mechanis-
tic approaches are increasingly being facilitated by ‘the wave
of research ‘in the epileptics [4]. The search continues for the
ideal drug that should be potent, selective in raising seizure
threshold and preventing seizure spread without causing se-
rious side effects.
Aryl acid hydrazones also possesses hydrophobic group
in close proximity to two electron donor nitrogen atoms,
hence may exhibit structural similarities with aryl semicar-
bazones. They can also interact with the proposed macromo-
lecular complex in vivo in the manner similar to aryl semi-
carbazones. This new aspect might be useful in designing
prototypic molecule with potential anticonvulsant activity. In
this study, a major change has been made to explore the pos-
sible anticonvulsant activities of aryl acid hydrazones.
A cyclic terpene, (±) 3-menthone has been selected to
satisfy the requirements of hydrophobic–hydrophilic site,
thus controlling pharmacokinetic properties. Earlier studies
of (±) 3-menthone and its derivatives have shown marked
anticonvulsant activity. The essential oil containing men-
thone from flower heads of Egletes viscosa, was reported to
possess significant protection in scPTZ test [9].
Majority of the currently used anti-epileptics contains
common structural features, such as hydrazones (=N-NH-),
amides (-CONH2), carbamides (-NHCONH-) and semicar-
bazido groups (=NNHCONH-). Semicarbazones have al-
ready acquired an important place as anticonvulsants and is a
new class of anticonvulsants with oral activity [5]. Semicar-
bazones displaying anticonvulsant properties were proposed
A ten carbon amino acid derived from hydrolysis of (-)
menthone oxime exhibits structural similarities with gamma
amino butyric acid (GABA) and has shown potent inhibition
of GABA neuroceptor [10]. In earlier studies on anticonvul-
sant properties of menthone and its derivatives, our research
group have reported antiepileptic properties of Schiff bases
of (±) 3-menthone with aryl amines and aryl semicarbazides
and thiosemicarbazides of menthone. Schiff bases were
found to possess significant protection in MES screen [11]
whereas aryl semicarbazides and thiosemicarbazides of (±)
3-menthone displayed significant anticonvulsant activity in
*Address correspondence to this author at the Department of Pharmacy,
RamEesh Institute of Vocational and Technical Education, 3, Knowledge
Park I, Greater Noida, Gautam Budh Nagar, Uttar Pradesh, India-201308,
India; Tel: +91 120 6589439; Fax: +91 120 2322656;
E-mail: jainendrem@yahoo.com
1573-4064/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

Menthone Aryl Acid Hydrazones
Medicinal Chemistry, 2011, Vol. 7, No. 1 57
both MES and scPTZ screen [7]. One of the derivatives, N1-
(4-fluorophenyl)-N4-(menth-3-one) semicarbazide has shown
MESED50 of 44.15 mg/kg and scPTZED50 of 38.68 mg/kg at
0.25h duration. All these data signifies the potential anticon-
vulsant properties of (±) 3-menthone which can be further
modified with suitable substitutions.
CH3
CH3
K2Cr2O7
H2SO4
OH
CH3
O
CH3
H3C
H3C
In addition, (±) 3-menthone derivatives have also been
reported to possess significant analgesic, sedative-hypnotic
and anti-HIV activities [12, 13].
(a)
Ar
Hence to further potentiate the anticonvulsant effects of
(±) 3-menthone, aryl acid hydrazones were synthesized and
evaluated for anticonvulsant activity with the aim of better
and safer anti-seizure profile.
DMF
CH3
HN
O
NH2
2. RESULTS AND DISCUSSION
2.1. Synthesis
H
N
Ar
N
CH3
The synthesis of (±) 3-menthone aryl acid hydrazones
was accomplished as presented in Scheme 1. (±) 3-menthone
(a) was prepared from oxidation of (-) menthol by chromic
acid method. The substituted aryl acid hydrazones were syn-
thesized by reaction between (±) 3-menthone and substituted
aryl acid hydrazides. Physicochemical properties of the syn-
thesized compounds are presented in Table 1. The structures
O
H3C
(Compound J1 - J10
)
Scheme 1. Synthesis of Menthone aryl acid hydrazones.
1
were characterized by spectral analyses (IR and HNMR).
The analytical data are presented in Table 2.
screens using doses of 30, 100 and 300mg/kg and observa-
tions were carried out at two different time intervals (0.5h
and 4.0h). These data are presented in Table 3. Compounds
J2, J3, J4 and J6 showed anti-MES activity indicating their
ability to prevent seizure spread. Compounds that showed
protection in MES model at 100mg/kg include J2, J3 and J4
whereas compound J6 showed activity at 300mg/kg. Com-
pounds J3 and J4 showed activity at both time intervals of
2.2. Pharmacological Activity
The newly synthesized derivatives (J1-J10) obtained from
the reaction sequence were injected intraperitoneally into
mice and evaluated in the maximal electroshock (MES),
subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity
Table 1. Physical Data of Synthesized Compounds
CH3
H
N
Ar
N
O
H3C
CH3
Comp No.
Ar
Yield (%)
m.p (°C)
Mol. Formula
Mol. wt.
Rf
logPa
J1
J2
J3
J4
J5
J6
J7
J8
J9
J10
Phenyl
28
40
15
10
85
33
40
22
17
71
92-4
120-2
285-7
111-3
119-1
119-1
99-1
C17H24N2O
C18H26N2O
C17H25N3O
C17H24N2O2
C17H23N3O3
C17H23ClN2O
C17H23BrN2O
C17H23FN2O
C16H23N3O
C16H23N3O
272
286
287
288
317
306
351
290
273
273
0.701
0.68
0.5
3.96
4.42
3.20
3.59
3.92
4.72
4.92
4.18
2.70
2.88
4-methyl phenyl
4-aminophenyl
4-hydroxyphenyl
4-nitrophenyl
4-chlorophenyl
4-bromophenyl
4-fluorophenyl
4-pyridyl
0.70
0.9
0.8
0.2
111-3
73-5
0.4
0.4
3-pyridyl
82-4
0.73
alogP was generated using ACD Chemsketch 12.0 software.

58 Medicinal Chemistry, 2011, Vol. 7, No. 1
Jain et al.
Table 2. Analytical Data of Some Synthesized Compounds
Comp No.
Chemical Name
Analytical Data
IR (KBr, cm-1): 3288, 3109, 2991, 1666, 1541, 1487. 1H NMR (DMSO d6) δ (ppm):
0.960 (s, 9H, 3CH3), 1.70-1.94 (m, 6H, 2CH2), 2.029 (br s, 1H, CH) 2.501 (br s, 1H,
CH), 2.712 (br s, 1H, CH), 7.57-7.59 (m, 5H, ArH), 10.32 (s, 1H, =NNH).
J1
N'-[5-methyl-2-(propan-2-yl) cyclohexylidene] ben-
zohydrazide
IR (KBr, cm-1): 3210, 3091, 2970, 2850, 1668, 1581, 1520, 791. 1H NMR (DMSO d6)
δ (ppm): 0.89-0.94 (t, 6H, 2xCH3), 0.99-1.01 (d, 3H, CH3, J=6.2), 1.65-1.73 (m, 2H,
CH2), 1.84- 2.00 (m, 3H, CH2&CH), 2.14-2.19 (m, 1H, CH), 2.35 (s, 3H, CH3), 2.57-
2.62 (m, 1H, CH), 7.31 (d, 2H, ArH), 7.67 (d, 2H, ArH), 10.42 (s, 1H, =N-NH).
J2
4-methyl-N'-[-5-methyl-2-(propan-2-yl) cyclo-
hexylidene]benzohydrazide
IR (KBr, cm-1): 3350, 3155, 2921, 2812, 1670, 1560, 1475, 715. 1H NMR (DMSO
d6) δ (ppm): 0.809-0.855 (d, 2H, CH2, J=13.8), 0.972 (br s, 7H, 2CH3, 1CH),
1.282-1.393 (m, 2H, CH2), 1.554 (br s, 2H, CH2), 1.717-1.822 (m, 1H, CH), 1.901
(br s, 3H, CH3), 2.780 (br s, 1H, CH), 5.695 (s, 2H, NH2), 6.607-6.630 (d, 2H, ArH,
J=6.9), 7.595-7.661 (d, 2H, ArH, J=7.8), 10.24-10.30 (m, 1H, =NNH).
J3
4-amino-N'-[5-methyl-2-(propan-2-
yl)cyclohexylidene] benzohydrazide
1
IR (KBr, cm-1): 3350, 3155, 2921, 2812, 1670, 1560, 1475, 715. H NMR (DMSO
J4
4-hydroxy-N'-[5-methyl-2-(propan-2-
yl)cyclohexylidene]benzohydrazide
d6) δ (ppm): 0.983-1.054 (m, 6H, 3xCH2), 1.282-2.025 (br m, 9H, 3xCH3), 2.270-
2.314 (m, 1H, CH), 2.541-2.599 (m, 1H, CH), 2.650-2.684 (m, 1H, CH), 7.007-
7.035 (d, 2H, ArH, J=8.4), 7.396-7.420 (d, 1H, ArH, J=7.2), 7.931-7.986 (m, 1H,
ArH), 11.026-11.144 (br s, 1H, ArOH), 11.838 (br s, 1H, =NNH).
IR (KBr, cm-1): 3166, 2985, 2870, 1688, 1581, 1529, 1352, 798. 1H NMR (DMSO
d6) δ (ppm): 0.922-0.938 (d, 5H, CH3 & CH2, J=4.8), 1.18-1.195 (m, 2H, CH2),
2.048-2.076 (m, 5H, CH3 & CH2), 2.202-2.218 (m, 1H, CH), 2.491 (s, 3H, CH3),
2.709-2.719 (m, 1H, CH), 8.02-8.048 (d, 2H, ArH, J=8.4), 8.266-8.288 (d, 2H, ArH,
J=6.6), 10.84 (br s, 1H, =NNH).
J5
N'-[5-methyl-2-(propan-2-yl)cyclohexylidene]-4-
nitrobenzohydrazide
IR (KBr, cm-1): 3295, 2912, 2850, 1670, 1552, 1487, 690. 1H NMR (DMSO d6) δ
(ppm):, 0.970 (s, 9H, 3CH3), 1.73-1.94 (m, 6H, 3CH2), 2.031 (br s, 1H, CH), 2.55
(br s, 1H, CH), 2.88 (br s, 1H, CH), 7.57-7.59 (d, 2H, ArH, J=7.2), 7.88-7.90 (d,
2H, ArH, J=7.5), 10.77 (s, 1H, =NNH).
J6
4-chloro-N'-[5-methyl-2-(propan-2-
yl)cyclohexylidene]benzohydrazide
IR (KBr, cm-1): 3122, 3012, 2891, 1676, 1598, 1411, 572. 1H NMR (DMSO d6) δ
(ppm):, 0.981 (s, 9H, 3CH3), 1.882-1.942 (m, 6H, 3CH2), 2.131 (br s, 1H, CH),
2.657 (br s, 1H, CH), 2.921 (br s, 1H, CH), 7.672-7.691 (d, 2H, ArH, J=6.8), 7.91-
7.93 (d, 2H, ArH, J=7.2), 10.91 (s, 1H, =NNH).
J7
4-bromo-N'-[5-methyl-2-(propan-2-
yl)cyclohexylidene]benzohydrazide
IR (KBr, cm-1): 3207, 3015, 2895, 1668, 1581, 1529. 1H NMR (DMSO d6) δ
(ppm):0.945-0.953 (d, 5H, CH3 & CH2, J=4.8), 1.191-1.202 (m, 2H, CH2), 2.121-
2.142 (m, 5H, CH3 & CH2), 2.310-2.326 (m, 1H, CH), 2.513 (s, 3H, CH3), 2.721-
2.732 (m, 1H, CH), 8.061-8.068 (d, 2H, ArH, J=8.1), 8.301-8.306 (d, 2H, ArH,
J=6.9).
J10
N'-[5-methyl-2-(propan-2-
yl)cyclohexylidene]pyridine-3-carbohydrazide
Table 3. Anticonvulsant Activity and Minimal Motor Impairment Studies of (±) 3-menthone Aryl Acid Hydrazones
Intraperitoneal Injection in Micea
Compd. No.
MES screen
scPTZ screen
Neurotoxicity screen
0.5h
4.0h
0.5h
4.0h
0.5h
4.0h
J1
J2
J3
J4
J5
J6
-
-
-
100
100
100
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
100
100
-
100
300
300
-
100
300
300
-
300
-

Menthone Aryl Acid Hydrazones
Medicinal Chemistry, 2011, Vol. 7, No. 1 59
Table 3. contd….
Intraperitoneal Injection in Micea
scPTZ screen
Compd. No.
MES screen
Neurotoxicity screen
0.5h
4.0h
0.5h
4.0h
0.5h
4.0h
J7
J8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
J9
J10
a Doses of 30, 100 and 300 mg/kg were administered. The figures in the table indicate the minimum dose whereby bioactivity was demonstrated in half or more of the mice. (-) indi-
cates absence of activity at maximum dose administered (300mg/kg).
0.5h and 4.0h. Compound J2 was found to be active at 4.0h
while compound J6 showed activity at 0.5h time interval.
The activity of compounds J3 and J4 have indicated longer
duration of action. All synthesized compounds were found to
inactive in scPTZ screen, a test used to identify compounds
that elevate seizure threshold.
did not show any neurotoxicity up to 500mg/kg, further indi-
cating better safety profile. The compound displayed excel-
lent protective index value (pI) [compound J6, pI > 32] as
compared to previously reported analogs of (±)-3-menthone
i.e. N1-(4-fluoro phenyl)-N4-(menth-3-one) semicarbazide
(pI = 1.22). This value was found to be even better than the
standard antiepileptic drug, Phenytoin (pI = 6.9) [14].
In the neurotoxicity screen, compounds J2 and J6 were
found to be non toxic whereas compounds J3 and J4 have
shown toxicity at 100mg/kg and 300mg/kg respectively.
Compound J6 was further screened in minimal clonic seizure
test at 6Hz and the data is presented in Table 4. The com-
pound displayed 100% protection in the dose of 50mg/kg
and 100mg/kg. At 100mg/kg compound J6 showed excellent
protection even up to 2.0h indicating longer duration of ac-
tion and hence it was further subjected to MES ED50 deter-
minations (6Hz) in mice at 0.25h time interval. The data is
shown in Table 5. The data showed MES ED50 of 16.1 ± 1.8
mg/kg. The compound was also screened for anticonvulsant
activity by oral administration to rats as shown in Table 6. It
has shown MES ED50 of 31.4 ± 0.7 mg/kg at 0.5h time inter-
val; however no protection was observed in scPTZ screen
even up to 250 mg/kg. As shown in Table 6, compound J6
Thus the present study revealed that halogen substituted
aryl acid hydrazones of (±) 3-menthone particularly chloro
substituted derivative showed a broad spectrum of anticon-
vulsant activity with non-neurotoxicity as compared to other
reported analogs of (±) 3-menthone. Hence halogen substi-
tuted menthone aryl acid hydrazones could be considered as
a lead compound in anticonvulsant drug development.
3. EXPERIMENTAL
3.1. Chemistry
Melting points were determined with a Veego India Digi-
tal Melting point apparatus and are reported uncorrected.
Infrared (IR) spectra were recorded for the compounds on
1
Shimadzu FTIR spectrophotometer 8400s (KBr). H NMR
Table 4. Anticonvulsant Activity of Compound J6 at 6Hz
Time (hrs)
0.25
0.5
1.0
2.0
4.0
Test
Dose (mg/kg)
25
50
3/4
4/4
4/4
1/4
4/4
4/4
0/4
-
0/4
-
0/4
-
MES
100
4/4
4/4
0/4
The figure indicates the number of mice out of four which were protected
Table 5. Evaluation of Compound J6 for MES ED50 in Mice at 6 Hz
Test
Time (hrs)
Dose (mg/kg)
No of Mice Protected
ED50 (mg/kg)
6.0
0/8
3/8
4/8
7/8
12.5
18.0
25.0
MES, 6Hz
0.25
16.1±1.8
The figure indicates the number of mice out of eight which were protected

60 Medicinal Chemistry, 2011, Vol. 7, No. 1
Jain et al.
3.2.1. Anticonvulsant Screening
Table 6. Rat Per Oral Quantification Studies of Compound
J6
The anticonvulsant evaluations were undertaken by the
Anticonvulsant Screening Program, National Institute of
Neurological Disorders and Stroke (NINDS), National Insti-
tute of Health, using their reported procedures [15, 16]. Ini-
tially all compounds were administered i.p. at doses of 30,
100 and 300mg/kg to one to four mice. Activity was estab-
lished using MES and scPTZ tests. Some selected deriva-
tives described in this study were also examined in minimal
clonic seizure test at 6Hz. One of the derivatives (compound
J6) was also examined in rat per oral test.
Test
Time (hrs)
ED50 (mg/kg)
MES, 6Hz
scPTZ
0.5
0.5
31.4±0.7
>250
Toxicity
>500
spectra were recorded in CDCl3 on a Brucker Avance
300MHz spectrometer. Chemical shifts were expressed in
parts per million (δ) with tetramethylsilane as an internal
standard. The purity of the compounds was monitored by
ascending thin layer chromatography (TLC) on silica gel G
(Merck) coated aluminum plates, visualized by iodine va-
pors. Developing solvent used in TLC was chloroform:ethyl
acetate (1:1). LogP values for all synthesized compounds
were calculated using ACD ChemSketch 12.0 software.
3.2.2. Neurotoxicity Screening
Minimal motor impairment was measured in mice by the
rotarod test [17]. The mice were trained to stay on an accel-
erating rotarod that rotates at 10 rpm. The rod diameter was
3.2cm. Trained animals were given i.p. injections of the test
compounds in doses of 30, 100 and 300mg/kg. Neurotoxicity
was indicated by the inability of the animal to maintain equi-
librium on the rod for at least 1.0min in each of three trials.
3.1.1. Synthesis of (±) 3-menthone (a)
ACKNOWLEDGEMENTS
Potassium dichromate (60.0g, 0.2mol) was dissolved in
300ml of distilled water. Concentrated Sulfuric acid (27.0ml,
0.27mol) was added with continuous stirring. (-) menthol
crystals (50g, 0.32mol) were added in portions with continu-
ous stirring. The reaction mixture was heated at 55°C for
15min. After cooling, menthone was extracted with solvent
ether (100ml, 3 times). The ethereal layer was washed with
5% Sodium Hydroxide solution followed by distilled water.
The ethereal layer was dried over anhydrous Sodium Sulfate
and menthone was purified by distillation under reduced
pressure, b.p 207-9°C, IR (KBr) νmax 2950, 1710, 1450, 1360
cm-1; 1H NMR (CDCl3) δ: 0.85-0.95 (br m, 9H, 3CH3), 1.27-
1.37 (m, 2H, CH2), 1.97-2.05 (m, 2H, CH2), 2.06-2.13 (m,
2H, CH2 adjacent to C=O), 2.27-2.32 (m, 1H, CH adjacent to
C=O).
The authors are thankful to the Director, Department of
Pharmaceutical Technology, Meerut Institute of Engineering
and Technolgy, Meerut, Uttar Pradesh, India for providing
necessary infrastructure for undertaking the project. One of
the authors James Stables deeply acknowledges NINDS,
NIH, Bethesda, MD, USA for undertaking the pharmacol-
ogical screening of synthesized compounds. The authors are
also thankful to Mr. M.N.Lal, IIT, Delhi, for the generation
of spectral data.
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To a solution of substituted aryl acid hydrazides in N, N-
dimethyl formamide (DMF, 0.05 mol), (±) 3-menthone (7.7
ml, 0.05 mol) was added and the reaction mixture was re-
fluxed on water bath for 10.0 hrs as described in Scheme 1.
The reaction was monitored by TLC using silica gel G lay-
ers. Excess solvent was evaporated under reduced pressure
and the synthesized compounds were further purified by col-
umn chromatography using silica gel (60-200 #) stationary
phase and mixture of chloroform: ethyl acetate (9:1) as mo-
bile phase. The excess solvent was evaporated under reduced
pressure and the precipitate was collected. The synthesized
products were dried at low temperatures in oven.
[6]
[7]
[8]
3.2. Pharmacology
[9]
Male albino mice (CF-1, strain, 18-25g) and male albino
rats (Sprague-Dawley/Wistar, 100-150g) were used as ex-
perimental animals. The animals were housed in metabolic
cages and allowed free access to food and water. The synthe-
sized compounds (1-7) were suspended in 0.5% methyl cel-
lulose/water mixture or in polyethylene glycol (PEG 200).
[10]

Menthone Aryl Acid Hydrazones
Medicinal Chemistry, 2011, Vol. 7, No. 1 61
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Jain, J. S.; Srivastava, R. S.; Aggrawal, N.; Sinha, R. Synthesis and
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[12]
[13]
Received: August 20, 2010
Revised: October 21, 2010
Accepted: November 01, 2010