Anti-inflammatory and Anti-nociceptive Activity of Ruthenium Complexes with Isonicotinic and Nicotinic Acids (Niacin) as Ligands

Autor(es)

Freitas, Cristina S. ^[1] ; Roveda, Antonio C. ^[2] ; Truzzi, Jr., Daniela R. ^[2] ; Garcia, Andre C. ^[2] ; Cunha, Thiago M. ^[1] ; Cunha, Fernando Q. ^[1] ; Franco, Douglas W. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, BR-14049900 Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Medicinal Chemistry; v. 58, n. 11, p. 4439-4448, JUN 11 2015.
• Citações Web of Science: 9

Resumo

This work evaluated the analgesic and anti-inflammatory activity of ruthenium(II) complexes trans-{[}Ru(NO+)(NH3)(4)(L)](BF4)(3) and {[}Ru(NH3)(5)(L)](BF4)(3) containing the nonsteroidal anti-inflammatory drugs nicotinic acid (Hnic) and its isomer isonicotinic acid (ina) as ligands (L). The anti-nociceptive potential of these complexes and the free ligands (noncoordinated to ruthenium) was tested in different models with doses ranging from 1 to 100 mu mol/kg. The ligands themselves were inactive; however, the ruthenium complexes containing Hnic and ina inhibited mechanical hyperalgesia induced by prostaglandin E-2, carrageenan-induced hyperalgesia, and antigen-induced arthritis. Moreover, the ruthenium complexes inhibited overt nociception induced by formalin, acetic acid, capsaicin, and cinnamaldehyde. The mechanism involved in the anti-nociceptive effects of the ruthenium complexes suggested that ATP-sensitive K+ channel pathways were not involved because glibenclamide did not affect their anti-nociceptive activities. However, the anti-nociceptive effect appears to be a consequence of the reduction in neutrophil migration and inhibition of the protein kinase C pathway. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/23651-4 - Nitrosilo e nitroxila como ligantes em Ru(II): síntese, reatividade, cinética e termodinâmica
• Beneficiário: Douglas Wagner Franco
• Linha de fomento: Auxílio à Pesquisa - Regular