Antinociceptive properties and nitric oxide synthase inhibitory action of new ruthenium complexes

Beirith, Alessandra; Creczynski-Pasa, Tânia B.; Bonetti, Vilson R; Konzen, Marlon; Seifriz, Ilana; Paula, Marcos S; Franco, Carlos; Calixto, João B.

doi:10.1016/s0014-2999(99)00095-3

Cited by 15 publications

(20 citation statements)

References 29 publications

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“…One hundred fifty microliters of parasite suspension was added to 96-well plates and incubated at 28°C for 72 h in the presence or absence of the substitution-containing chalcones (3 to 1,000 M), amphotericin B (10.8 to 1,082.0 nM; used as a control), or benznidazole (10 to 1,000 M; used as a control). Three to four experiments were carried out in triplicate, and the number of surviving parasites was determined in Neubauer chambers.The cytotoxic activity of substitution-containing chalcones to mouse peritoneal macrophages was evaluated as previously described (1,17). To this end, cells were harvested from the peritonea of mice 2 to 3 days after injection of 2 ml of sterile thioglycolate solution (3% [wt/vol] in water).…”

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Trypanocidal and Leishmanicidal Properties of Substitution-Containing Chalcones

Lunardi

Guzela

Rodrigues

et al. 2003

Antimicrob Agents Chemother

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Ten chalcones were synthesized and tested as potential leishmanicidal and trypanocidal agents. All tested compounds caused concentration-dependent inhibition of the in vitro growth of Leishmania braziliensis and Trypanosoma cruzi with no significant toxic effect towards host macrophages. Our results show that the positions of the substituents seem to be critical for their antiprotozoal activities.Among the kinetoplastid protozoa, which infect invertebrates, mammals, and plants, some species are of particular interest due to their medical importance. These include Trypanosoma cruzi (the agent of Chagas' disease), the African trypanosome responsible for sleeping sickness, and several species of Leishmania, which cause the various forms of leishmaniasis (9). The World Health Organization has identified Chagas' disease and leishmaniasis as major and increasing public health problems, particularly in Latin America (14,15,16,18). In spite of the socioeconomic importance of these tropical infectious diseases, efforts directed towards the discovery of new drugs and/or vaccines against them are underdeveloped (10, 13). In addition, most of the drugs currently in use (i) were developed several decades ago, (ii) show variable efficacy, (iii) have serious side effects, (iv) are expensive, (v) can require long-term treatment, (vi) may have low activity in immunosuppressed patients, and (vii) present and/or induce resistance in parasites (9, 10, 16). Thus, the need for the development of new, effective, cheap, and safe drugs for the treatment of leishmaniasis and Chagas' disease is very important.Chalcones, or 1,3-diaryl-2-propen-1-ones, are natural or synthetic compounds belonging to the flavonoid family. Chalcones possess a broad spectrum of biological activities, including antibacterial, anthelmintic, amoebicidal, antiulcer, antiviral, insecticidal, antiprotozoal, anticancer, cytotoxic, and immunosuppressive activities (for reviews, see references 11 and 12). The present study was designed to determine the in vitro leishmanicidal and trypanocidal activities of the 10 substitutioncontaining chalcones and to investigate the cytotoxic effects of these chalcones on mouse peritoneal macrophages in vitro.The chalcones used in the present study were synthesized in our laboratory by reaction of the appropriate aryl methyl ketone and aryl aldehyde (in a 1:1 ratio) in the presence of sodium hydroxide and ethanol. The products were then added to cooled diluted acetic acid according to the methodology previously described (8). The synthetic reaction gave substantial yields (55 to 98%) of all the chalcones, and these were characterized by 1 H nuclear magnetic resonance and infrared analyses and by microanalysis. The substitution-containing chalcones were dissolved in 0.5% Tween 80 in phosphatebuffered saline to prepare a working solution with a 0.1 M concentration before being passed through 0.22-m-pore-size Millipore filters. The structures of the chalcones are shown in Table 1.Cultures of promastigote forms of Leishmania braziliensis...

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“…The cytotoxic activity of substitution-containing chalcones to mouse peritoneal macrophages was evaluated as previously described (1,17). To this end, cells were harvested from the peritonea of mice 2 to 3 days after injection of 2 ml of sterile thioglycolate solution (3% [wt/vol] in water).…”

mentioning

confidence: 99%

Trypanocidal and Leishmanicidal Properties of Substitution-Containing Chalcones

Lunardi

Guzela

Rodrigues

et al. 2003

Antimicrob Agents Chemother

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“…The synthetic chemistry of transition metals complexes has been the main focus of several research groups, with special attention on the therapeutic potential and biological action of these compounds [1][2][3][4][5]. One of these transition metals complexes, ruthenium, it's very interesting because the properties of these compounds can be altered by the choice of the ligand, which means that complexes potentially have multiple applications [2,4,5].…”

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confidence: 99%

“…One of these transition metals complexes, ruthenium, it's very interesting because the properties of these compounds can be altered by the choice of the ligand, which means that complexes potentially have multiple applications [2,4,5]. Many biological properties have been attributed to ruthenium complexes including, for example, antioxidant activity [6].…”

Section: Introductionmentioning

confidence: 99%

“…The physiological effects of NO are attributed to small size, large diffusion potential, and potent action as a free radical [12][13][14]. Previous studies in our lab with trans-[RuCl 2 (nic) 4 ] and trans-[RuCl 2 (i-nic) 4 ] complexes were performed to evaluates the action of this compounds with nitric oxide isoenzymes [4]. Complex II inhibited neuronal and inducible nitric oxide synthase.…”

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Pharmacological Activity of Ruthenium Complexes trans-[RuCl2(L)4] (L = Nicotinic or i-Nicotinic acid) on Anxiety and Memory in Rats

et al. 2006

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Many biological properties have been attributed to ruthenium complex I (trans-[RuCl(2)(nic)(4)]) and ruthenium complex II (trans-[RuCl(2 )(i-nic)( 4)]) including nitric oxide synthase inhibition. In this study, we evaluated pharmacological effects of these complexes on anxiety and memory formation. Memory was evaluated with inhibitory avoidance and habituation to an open-field and anxiety was tested with elevated plus-maze. Adult male Wistar rats (250 to 350 g) received intraperitoneal injections of vehicle, ruthenium complex I (45.2, 90.4, or 180.7 mumol/kg), or ruthenium complex II (0.08, 4.5, or 13.6 mumol/kg) 30 min prior open-field training or elevated plus-maze test and 30 min or 0 h after training. No effects were observed in the anxiety parameters and habituation to an open-field. The ruthenium complexes impaired memory retention compared with vehicle group in the inhibitory avoidance, as when administrated 30 min prior as immediately after training. The memory impairment induced by ruthenium complexes may be due to their nitric oxide synthase inhibition capacity.

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The role of nitric oxide in nociception

Luo

Cizkova

2000

Current Review of Pain

144

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Pharmacologic, electrophysiologic, and immunohistochemical studies have suggested a role of nitric oxide (NO) in nociception processing. Recent studies have indicated that NO may modulate spinal and sensory neuron excitability through multiple mechanisms that may underlie its distinctive roles in different pain states. Differential regulation of a family of NO-producing enzymes, NO synthases, contributes mainly to the complexity underlying the role of NO in nociception. This review summarizes the latest advances in our understanding of the contribution of NO to pain transduction. Possible cellular mechanisms regarding the connection between NO production and the abnormal sensation derived from different stimuli and pathologic conditions are discussed.

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Antinociceptive properties and nitric oxide synthase inhibitory action of new ruthenium complexes

Cited by 15 publications

References 29 publications

Trypanocidal and Leishmanicidal Properties of Substitution-Containing Chalcones

Trypanocidal and Leishmanicidal Properties of Substitution-Containing Chalcones

Pharmacological Activity of Ruthenium Complexes trans-[RuCl2(L)4] (L = Nicotinic or i-Nicotinic acid) on Anxiety and Memory in Rats

The role of nitric oxide in nociception

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