ArticleAntimicrobial agents and chemotherapy2014
Nitro/nitrosyl-ruthenium complexes are potent and selective anti-Trypanosoma cruzi agents causing autophagy and necrotic parasite death.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 28 citations in OpenAlex.
- Ruthenium Complexes Containing Thiobenzamide Act as Potent and Selective Anti-ACS infectious diseases · 2026Article
- Ruthenium Complexes in the Fight against Pathogenic Microorganisms. An Extensive Review.Pharmaceutics · 2021Review
- Article
- Dibenzylideneacetones Are Potent Trypanocidal Compounds That Affect the Trypanosoma cruzi Redox System.Antimicrobial agents and chemotherapy · 2016Article
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Authors and funding
10 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
cis-[RuCl(NO2)(dppb)(5,5'-mebipy)] (complex 1), cis-[Ru(NO2)2(dppb)(5,5'-mebipy)] (complex 2), ct-[RuCl(NO)(dppb)(5,5'-mebipy)](PF6)2 (complex 3), and cc-[RuCl(NO)(dppb)(5,5'-mebipy)](PF6)2 (complex 4), where 5,5'-mebipy is 5,5'-dimethyl-2,2'-bipyridine and dppb is 1,4-bis(diphenylphosphino)butane, were synthesized and characterized. The structure of complex 2 was determined by X-ray crystallography. These complexes exhibited a higher anti-Trypanosoma cruzi activity than benznidazole, the current antiparasitic drug. Complex 3 was the most potent, displaying a 50% effective concentration (EC50) of 2.1 ± 0.6 μM against trypomastigotes and a 50% inhibitory concentration (IC50) of 1.3 ± 0.2 μM against amastigotes, while it displayed a 50% cytotoxic concentration (CC50) of 51.4 ± 0.2 μM in macrophages. It was observed that the nitrosyl complex 3, but not its analog lacking the nitrosyl group, releases nitric oxide into parasite cells. This release has a diminished effect on the trypanosomal protease cruzain but induces substantial parasite autophagy, which is followed by a series of irreversible morphological impairments to the parasites and finally results in cell death by necrosis. In infected mice, orally administered complex 3 (five times at a dose of 75 μmol/kg of body weight) reduced blood parasitemia and increased the survival rate of the mice. Combination index analysis of complex 3 indicated that its in vitro activity against trypomastigotes is synergic with benznidazole. In addition, drug combination enhanced efficacy in infected mice, suggesting that ruthenium-nitrosyl complexes are potential constituents for drug combinations.
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