New uses for old complexes: The very first report on the trypanocidal activity of symmetric trinuclear ruthenium complexes

Autor(es)

Possato, Bruna ^[1] ; Carneiro, Zumira Aparecida ^[2] ; de Albuquerque, Sergio ^[2] ; Nikolaou, Sofia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Preto, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 176, p. 156-158, NOV 2017.
• Citações Web of Science: 1

Resumo

This work reports on the trypanocidal activity of a series of symmetric triruthenium complexes combined with azanaphthalene ligands of general formula {[}Ru3O(CH3COO)(6)(L)(3)]PF6 (L = (1) quinazoline (qui), (2) 5-nitroisoquinoline (5-nitroiq), (3) 5-bromoisoquinoline (5-briq), (4) isoquinoline (iq), (5) 5-aminoisoquinoline (5-amiq), and (6) 5,6,7,8-tetrahydroisoquinoline (thiq)). All complexes within the series presented in vitro trypanocidal activity against both the trypomastigote and amastigote forms of T. cruzi. The IC50 values obtained for complexes 1-6 ranged from 1.39 to 165.9 mu M for the trypomastigote form and from 1.06 to 53.16 mu M for the amastigote form. These values were lower than the values observed for the metallic core {[}Ru3O (CH3COO)(6)(CH3OH)(3)](+) itself and for the free ligands in all cases. Remarkably, complex 6 displayed lower IC50 values than the reference drug (benznidazole) for the acute (trypomastigote form) and chronic (amastigote form) phases of Chagas disease. These findings, combined with the low toxicity against healthy cells (LLK-MK2 strain) and a high SI value (Selectivity Index > 10) make complex 6 an excellent candidate for in vivo tests. (AU)

• Processo FAPESP: 13/18009-4 - Planejamento, síntese e atividade tripanossomicida de inibidores covalentes reversíveis da enzima cruzaína
• Beneficiário: Carlos Alberto Montanari
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/20302-7 - Uso de anti-inflamatórios não esteroidais, azanaftalenos e fenazinas como ligantes na obtenção de carboxilatos bi- e trinucleares de rutênio com potencial atividade antialérgica, tumoricida e tripanocida
• Beneficiário: Sofia Nikolaou
• Modalidade de apoio: Auxílio à Pesquisa - Regular