ArticleBritish journal of pharmacology2010
Nitric oxide donor trans-[RuCl([15]aneN)NO] as a possible therapeutic approach for Chagas' disease.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 53 citations in OpenAlex.
- Nitric oxide in parasitic infections: a friend or foe?Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Review
- Review on Experimental Treatment Strategies AgainstJournal of experimental pharmacology · 2021Review
- Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis.Nature communications · 2018Article
- Antileishmanial Activity and Inducible Nitric Oxide Synthase Activation by RuNO Complex.Mediators of inflammation · 2016Article
- Developments in the management of Chagas cardiomyopathy.Expert review of cardiovascular therapy · 2015Review
- Article
- In vitro Treatment with cis-[Ru(H-dcbpy-)2(Cl)(NO)] Improves the Endothelial Function in Aortic Rings with Endothelial Dysfunction.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2015Article
- Ruthenium complex with benznidazole and nitric oxide as a new candidate for the treatment of chagas disease.PLoS neglected tropical diseases · 2014Article
- Nitro/nitrosyl-ruthenium complexes are potent and selective anti-Trypanosoma cruzi agents causing autophagy and necrotic parasite death.Antimicrobial agents and chemotherapy · 2014Article
- Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease.Memorias do Instituto Oswaldo Cruz · 2014Article
- Article
- Challenges and perspectives of Chagas disease: a review.The journal of venomous animals and toxins including tropical diseases · 2013Article
- Experimental chemotherapy in paracoccidioidomycosis using ruthenium NO donor.Mycopathologia · 2011Article
- Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones.Molecular biology international · 2011Article
- Advances in Chagas disease drug development: 2009-2010.Current opinion in infectious diseases · 2010Review
- In vitro and in vivo trypanocidal effects of the cyclopalladated compound 7a, a drug candidate for treatment of Chagas' disease.Antimicrobial agents and chemotherapy · 2010Article
- New drugs for neglected infectious diseases: Chagas' disease.British journal of pharmacology · 2010Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeBenznidazole (Bz) is the therapy currently available for clinical treatment of Chagas' disease. However, many strains of Trypanosoma cruzi parasites are naturally resistant. Nitric oxide (NO) produced by activated macrophages is crucial to the intracellular killing of parasites. Here, we investigate the in vitro and in vivo activities against T. cruzi, of the NO donor, trans-[RuCl([15]aneN(4))NO](2+). EXPERIMENTAL APPROACH: Trans-[RuCl([15]aneN(4))NO](2+)was incubated with a partially drug-resistant T. cruzi Y strain and the anti-proliferative (epimastigote form) and trypanocidal activities (trypomastigote and amastigote) evaluated. Mice were treated during the acute phase of Chagas' disease. The anti-T. cruzi activity was evaluated by parasitaemia, survival rate, cardiac parasitism, myocarditis and the curative rate. KEY
resultsTrans-[RuCl([15]aneN(4))NO](2+) was 10- and 100-fold more active than Bz against amastigotes and trypomastigotes respectively. Further, trans-[RuCl([15]aneN(4))NO](2+) (0.1 mM) induced 100% of trypanocidal activity (trypomastigotes forms) in vitro. Trans-[RuCl([15]aneN(4))NO](2+) induced permanent suppression of parasitaemia and 100% survival in a murine model of acute Chagas' disease. When the drugs were given alone, parasitological cures were confirmed in only 30 and 40% of the animals treated with the NO donor (3.33 micromol.kg(-1).day(-1)) and Bz (385 micromol.kg(-1).day(-1)), respectively, but when given together, 80% of the animals were parasitologically cured. The cured animals showed an absence of myocarditis and a normalisation of cytokine production in the sera. In addition, no in vitro toxicity was observed at the tested doses. CONCLUSIONS AND IMPLICATIONS: These findings indicate that trans-[RuCl([15]aneN(4))NO](2+)is a promising lead compound for the treatment of human Chagas' disease.
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