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O.A. El-Gammal et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 120 (2014) 332–339
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bidities, and premature mortality. Consequently, development of
treatment strategies to bring the disease under control quickly is
of utmost importance [2]. Nonsteroidal anti-inflammatory drugs
(NSAIDs) are among the most widely used therapeutics, primarily
for the treatment of pain and inflammation, especially arthritis
[3]. Piroxicam is a nonsteroidal anti-inflammatory drug and it
has anti-inflammatory, analgesic and antipyretic activity [4]. The
role of zinc and copper in chronic inflammatory diseases is of inter-
est because they are co-factors of important enzymes involved in
collagen and bone metabolism [5,6] immune system function
[7,8] and antioxidant protection [9]. Furthermore, changes in
serum zinc and copper levels observed in RA patients led some
investigators to hypothesize that a marginal deficiency in zinc
and copper might contribute to the development of RA and to
the progression of the disease itself [10]. Also, it has been shown
that the inflammation associated with rheumatoid arthritis can
be reduced using copper complexes [11].Hydrazones are a versatile
class of compounds which present innumerous chemical and phar-
macological applications. They have shown to possess antimicro-
bial, anticonvulsant, analgestic, anti-inflammatory, antiplatelet,
antitubercular, antitumoral properties [12–15]. Literature survey
showed no pharmacological assay on the present hydrazone, 2-
(naphthalen-1-yloxy)-N0-(1-(pyridin-2-yl)ethylidene) acetohyd-
razide (HA2PNA) has yet been undertaken. So, this work aims to
study the anti-rhemuatic activity of the present hydrazone (HA2P-
NA) as well as its Cu(II) and Zn(II) complexes.
Synthesis of a-naphthoxyacetylhydrazine
a
-naphthoxyacetylhydrazine was synthesized by the literature
method [16]. A solution of ethyl -naphthoxyacetate (23 ml,
a
0.1 mol) and 100 ml of absolute ethanol were added to 5.0 ml of
hydrazine hydrate (0.1 mol) and the mixture was refluxed for
3 h. The obtained solution was evaporated to one third its original
volume. Then the product formed was cooled, filtered off, washed
several times with diethyl ether and finally dried over anhydrous
CaCl2; yield ꢂ16.2 gm; m.p: 158–160 °C.
Synthesisof2-(naphthalen-1-yloxy)-N0-(1-(pyridin-2-
l)ethylidene)acetohydrazide(HA2PNA)
2-(naphthalen-1-yloxy)-N0-(1-(pyridin-2-yl)ethylidene)acet-
ohydrazide (HA2PNA) was prepared by heating equimolar
amounts of 2-acetylpyridine (11 ml, 0.1 mol) and
thoxyacetylhydrazine (23.4 gm, 0.11 mol) in 150 ml absolute
ethanol under reflux for 2 h. On cooling, piege precipitate was
separated. The product was filtered off, washed, recrystallized
from absolute ethanol and finally dried in a vacuum desiccator
over anhydrous calcium chloride. Yield ꢂ25.4 gm, m.p. 180–
183 °C.
a-naph-
Synthesis of metal complexes
A hot ethanolic or aqueous ethanolic solution of the respective
metal acetate (1.0 mmol) was added to hot ethanolic solution of
HA2PNA (0.296 g, 1.0 mmol). The resultant mixture was heated
under reflux for 1 h. The precipitates that formed were filtered
off, washed with ethanol followed by diethyl ether and dried in a
vacuum desiccator over anhydrous CaCl2. The physical and analyt-
ical data of the isolated complexes are listed in Table 1. The com-
plexes are stable and readily soluble in DMF and DMSO. The
values of molar conductivity of all complexes, lie in the range (5–
7 ohmꢁ1 cm2 molꢁ1) indicating their non-electrolytic nature [17].
Experimental
Instrumentation and materials
All the chemicals were purchased from Aldrich and Fluka and
used without further purification. Elemental analyses (C, H, N)
were performed with a Perkin–Elmer 2400 series II analyzer. Molar
conductance values (10ꢁ3 mol lꢁ1) of the complexes in DMF were
measured using a Tacussel conductivity bridge model CD6NG. IR
spectra (4000–400 cmꢁ1) for KBr discs were recorded on a Mattson
5000 FTIR spectrophotometer. Electronic spectra were recorded on
a Unicam UV–visible spectrophotometer UV2. Magnetic suscepti-
bilities were measured with a Sherwood scientific magnetic sus-
ceptibility balance at 298 K. 1H NMR measurements in d6-DMSO
at room temperature were carried out on a Varian Gemini WM-
300 MHz spectrometer at the Microanalytical Unit, Cairo Univer-
sity. Thermogravimetric measurements (TGA, DTA, 20–1000 °C)
were recorded on a DTG-50 Shimadzu thermogravimetric analyzer
at a heating rate of 15 °C/min and nitrogen flow rate of 20 ml/min.
A powder ESR spectrum was obtained in a 2 mm quartz capillary at
room temperature with a Bruker EMX spectrometer working in the
X-band (9.78 GHz) with 100 kHz modulation frequency. The
microwave power and modulation amplitudes were set at 1 mW
and 4G, respectively. The low field signal was obtained after four
scans with 10-fold increase in the receiver again.
Pharmacological test
Animals
Fourty eight Sprague–Dawley rats (200–250 g) were fed on a
standard rat chow and water and labium. Animal care and experi-
ments were performed in accordance with NIH guide to the care
and use of laboratory animals. The local ethical committee ap-
proved the study. Rats were housed under similar standard labora-
tory conditions. The animals were divided into two main groups
[non arthritic control (n = 6) and arthritic group (n = 42)]. In the ar-
thritic group, all rats had been inoculated by the reagent of colla-
gen adjuvant arthritis into the left paw pad. Rats which
developed right paw arthritic manifestations after 45 days were
divided into seven groups each group contained 6 rats as follow,
arthritic control, piroxicam treated, zinc acetate treated, copper
acetate treated, (HA2PNA) treated, [Cu(A2PNA)2]H2O complex
Table 1
Analytical and physical data of HA2PNA and its metal complexes.
Compound empirical formula (F Wt)
Color
M.p. (°C)
% Found (Calcd.)
Yield (%)
M
Cl
C
H
(HA2PNA) C19H17N3O2 (296.33)
[Zn(A2PNA)(OAc)(H2O)] ZnC21H21N3O5 (460.76)
Grey
Grey
183
260
–
–
–
71.38 (71.46)
54.46
5.42 (5.37)
4.67
–
84
14.10
(14.19)
(54.74)
63.79
(4.59)
4.88
[Cu(A2PNA)2]H2O CuC38H34N6O5 (718.14)
Dark green
260
8.46
–
88
(8.38)
(63.55)
(4.77)