INQUISUR   21779
INSTITUTO DE QUIMICA DEL SUR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Anti-inflammatory properties of two new copper(II) complexes with Fenoprofen
Autor/es:
AGOTEGARAY, MARIELA A.; BOERIS, MÓNICA A.; QUINZANI, OSCAR VALENTÍN
Lugar:
Córdoba
Reunión:
Congreso; Primera Reunión Internacional de Ciencias Farmaceúticas (RICIFa 2010); 2010
Institución organizadora:
Universidad Nacional de Cordoba
Resumen:
Introduction
The proposed curative properties of copper based non-steroidal anti-inflammatory drugs
(NSAIDs) have led to the development of copper(II) complexes of NSAIDs with enhanced antiinflammatory
activity and reduced gastrointestinal toxicity compared with their uncomplexed
parent drugs. No copper(II) anti-inflammatory drug is currently available for oral human use,
although a gel base of copper-salicylate (Alcusal®) is available for topical temporal relief of pain an
inflammation in humans in Australia(1).
Copper is an essential trace element, taking part in all aspects of metabolism(2). It is
believed to possess anti-inflammatory activity and has been proposed an increased demand for
copper during inflammatory conditions(3).
Fenoprofen, 2-(3-phenoxyphenyl)propionic acid, is an antipyretic, analgesic and
NSAID(4). Little is known about chemical structures of Fenoprofen complexes and copper drugs
have yet to reach an extended human market, so in this work we present the enhanced antiinflammatory
activity of two new copper(II) complexes with Fenoprofen.®) is available for topical temporal relief of pain an
inflammation in humans in Australia(1).
Copper is an essential trace element, taking part in all aspects of metabolism(2). It is
believed to possess anti-inflammatory activity and has been proposed an increased demand for
copper during inflammatory conditions(3).
Fenoprofen, 2-(3-phenoxyphenyl)propionic acid, is an antipyretic, analgesic and
NSAID(4). Little is known about chemical structures of Fenoprofen complexes and copper drugs
have yet to reach an extended human market, so in this work we present the enhanced antiinflammatory
activity of two new copper(II) complexes with Fenoprofen.
Materials and Methods
Copper complexes, of formula Cu2(Fen)4(caf)2 and Cu(Fen)2(im)2 (Fen: Fenoprofenate; caf:
caffeine; im: imidazole), were synthesized from Cu2(Fen)4(dmf)2(5) dissolved in acetone and by the
addition of a solution of caffeine in ethanol and imidazole, in acetone respectively. The diffusion of
acetonitrile led to the formation of crystals which were studied by physicochemical techniques to
confirm their molecular structures.
The studies of the anti-inflammatory properties were carried out employing the
carrageenan induced paw oedema in female mice described by Winter et al(6).
Test animals were administered orally an aqueous suspension of Cu2(Fen)4(caf)2 (31
mg/kg), Cu(Fen)2(im)2 (28 mg/kg) and the calcium salt of Fenoprofen (21 mg/kg). The vehicle
alone (carboxymethylcellulose and Tween80) was used as excipient for the control group. Drug
and excipient were orally administered to each animal one-hour before inducing oedema in the left
hind paw by sub-plantar injection of carrageenan.
The length of the paw was measured with a digital electronic caliber immediately before
the injection of carrageenan and 3, 5, 7 and 9 hours after. The anti-inflammatory effect was
expressed in terms of the percent inhibition of oedema produced by each drug-treated group.2(Fen)4(caf)2 and Cu(Fen)2(im)2 (Fen: Fenoprofenate; caf:
caffeine; im: imidazole), were synthesized from Cu2(Fen)4(dmf)2(5) dissolved in acetone and by the
addition of a solution of caffeine in ethanol and imidazole, in acetone respectively. The diffusion of
acetonitrile led to the formation of crystals which were studied by physicochemical techniques to
confirm their molecular structures.
The studies of the anti-inflammatory properties were carried out employing the
carrageenan induced paw oedema in female mice described by Winter et al(6).
Test animals were administered orally an aqueous suspension of Cu2(Fen)4(caf)2 (31
mg/kg), Cu(Fen)2(im)2 (28 mg/kg) and the calcium salt of Fenoprofen (21 mg/kg). The vehicle
alone (carboxymethylcellulose and Tween80) was used as excipient for the control group. Drug
and excipient were orally administered to each animal one-hour before inducing oedema in the left
hind paw by sub-plantar injection of carrageenan.
The length of the paw was measured with a digital electronic caliber immediately before
the injection of carrageenan and 3, 5, 7 and 9 hours after. The anti-inflammatory effect was
expressed in terms of the percent inhibition of oedema produced by each drug-treated group.2(Fen)4(dmf)2(5) dissolved in acetone and by the
addition of a solution of caffeine in ethanol and imidazole, in acetone respectively. The diffusion of
acetonitrile led to the formation of crystals which were studied by physicochemical techniques to
confirm their molecular structures.
The studies of the anti-inflammatory properties were carried out employing the
carrageenan induced paw oedema in female mice described by Winter et al(6).
Test animals were administered orally an aqueous suspension of Cu2(Fen)4(caf)2 (31
mg/kg), Cu(Fen)2(im)2 (28 mg/kg) and the calcium salt of Fenoprofen (21 mg/kg). The vehicle
alone (carboxymethylcellulose and Tween80) was used as excipient for the control group. Drug
and excipient were orally administered to each animal one-hour before inducing oedema in the left
hind paw by sub-plantar injection of carrageenan.
The length of the paw was measured with a digital electronic caliber immediately before
the injection of carrageenan and 3, 5, 7 and 9 hours after. The anti-inflammatory effect was
expressed in terms of the percent inhibition of oedema produced by each drug-treated group.2(Fen)4(caf)2 (31
mg/kg), Cu(Fen)2(im)2 (28 mg/kg) and the calcium salt of Fenoprofen (21 mg/kg). The vehicle
alone (carboxymethylcellulose and Tween80) was used as excipient for the control group. Drug
and excipient were orally administered to each animal one-hour before inducing oedema in the left
hind paw by sub-plantar injection of carrageenan.
The length of the paw was measured with a digital electronic caliber immediately before
the injection of carrageenan and 3, 5, 7 and 9 hours after. The anti-inflammatory effect was
expressed in terms of the percent inhibition of oedema produced by each drug-treated group.2(im)2 (28 mg/kg) and the calcium salt of Fenoprofen (21 mg/kg). The vehicle
alone (carboxymethylcellulose and Tween80) was used as excipient for the control group. Drug
and excipient were orally administered to each animal one-hour before inducing oedema in the left
hind paw by sub-plantar injection of carrageenan.
The length of the paw was measured with a digital electronic caliber immediately before
the injection of carrageenan and 3, 5, 7 and 9 hours after. The anti-inflammatory effect was
expressed in terms of the percent inhibition of oedema produced by each drug-treated group.
Results
The study of acute anti-inflammatory test showed that the percentages of inhibition of
inflammation for Cu2(Fen)4(caf)2 were 84.3, 81.0, 81.5 and 73.4% at the third, fifth, seventh and
ninth hour from the beginning of the experiment, meanwhile for Cu(Fen)2(im)2, the percentages
were 30.0, 33.3, 58.5, 40.5% respectively. When Fenoprofen calcium salt was studied it presented
29.1, 42.3, 19.9, 10.5% of inhibition at the same hours.2(Fen)4(caf)2 were 84.3, 81.0, 81.5 and 73.4% at the third, fifth, seventh and
ninth hour from the beginning of the experiment, meanwhile for Cu(Fen)2(im)2, the percentages
were 30.0, 33.3, 58.5, 40.5% respectively. When Fenoprofen calcium salt was studied it presented
29.1, 42.3, 19.9, 10.5% of inhibition at the same hours.2(im)2, the percentages
were 30.0, 33.3, 58.5, 40.5% respectively. When Fenoprofen calcium salt was studied it presented
29.1, 42.3, 19.9, 10.5% of inhibition at the same hours.
Discussion
Cu2(Fen)4(caf)2 presented the highest inflammation inhibition percent, sustaining it during
all the time of the experiment. Cu(Fen)2(im)2 presented highest action than Fenoprofen salt from
the fifth hour. Both complexes maintained enhanced action until the end of the experiment when
compared to Fenoprofen calcium salt, demonstrating a more sustain activity in time.2(Fen)4(caf)2 presented the highest inflammation inhibition percent, sustaining it during
all the time of the experiment. Cu(Fen)2(im)2 presented highest action than Fenoprofen salt from
the fifth hour. Both complexes maintained enhanced action until the end of the experiment when
compared to Fenoprofen calcium salt, demonstrating a more sustain activity in time.2(im)2 presented highest action than Fenoprofen salt from
the fifth hour. Both complexes maintained enhanced action until the end of the experiment when
compared to Fenoprofen calcium salt, demonstrating a more sustain activity in time.
Conclusion
Both copper(II) complexes with Fenoprofen presented enhanced anti-inflammatory action
than the uncomplexed parent drug, being this characteristic improved for the complex containing
caffeine in its structure. Complementary studies, such as analgesic and toxicological effects are
being carried out to improve the knowledge of therapeutic properties of this kind of potential new
anti-inflammatory drugs.
References
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