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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 176, p. 156-158, NOV 2017.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 13/18009-4 - Molecular design, synthesis and trypanocidal activity of cruzain reversible covalent inhibitors
• Grantee: Carlos Alberto Montanari
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/20302-7 - Using non-steroidal antiinflammatory drugs, azanaphtalenes and phenazines as ligands for the development of bi- and trinuclear rutenium carboxylates with potential antialergic, tumoricide and tripanocide activities
• Grantee: Sofia Nikolaou
• Support type: Regular Research Grants