ArticleAntimicrobial agents and chemotherapy2007
Cellular effects of reversed amidines on Trypanosoma cruzi.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Experimental and Clinical Treatment of Chagas Disease: A Review.The American journal of tropical medicine and hygiene · 2017Review
- 3-Hydroxykynurenine, a Tryptophan Metabolite Generated during the Infection, Is Active AgainstACS medicinal chemistry letters · 2017Article
- Phenotypic evaluation and in silico ADMET properties of novel arylimidamides in acute mouse models ofDrug design, development and therapy · 2017Article
- Phenotypic Screening In Vitro of Novel Aromatic Amidines against Trypanosoma cruzi.Antimicrobial agents and chemotherapy · 2016Article
- Biological Efficacy and Toxicity of Diamidines in Myotonic Dystrophy Type 1 Models.Journal of medicinal chemistry · 2015Article
- Unveiling the effects of berenil, a DNA-binding drug, on Trypanosoma cruzi: implications for kDNA ultrastructure and replication.Parasitology research · 2015Article
- The in vitro biological activity of the Brazilian brown seaweed Dictyota mertensii against Leishmania amazonensis.Molecules (Basel, Switzerland) · 2014Article
- Studies on the antileishmanial mechanism of action of the arylimidamide DB766: azole interactions and role of CYP5122A1.Antimicrobial agents and chemotherapy · 2014Article
- In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi.Antimicrobial agents and chemotherapy · 2014Article
- Structure-dependent binding of arylimidamides to the DNA minor groove.Chembiochem : a European journal of chemical biology · 2014Article
- The double-edged sword in pathogenic trypanosomatids: the pivotal role of mitochondria in oxidative stress and bioenergetics.BioMed research international · 2014Review
- P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance.Parasitology research · 2013Article
- Di-cationic arylimidamides act against Neospora caninum tachyzoites by interference in membrane structure and nucleolar integrity and are active against challenge infection in mice.International journal for parasitology. Drugs and drug resistance · 2012Article
- Evaluation of arylimidamides DB1955 and DB1960 as candidates against visceral leishmaniasis and Chagas' disease: in vivo efficacy, acute toxicity, pharmacokinetics, and toxicology studies.Antimicrobial agents and chemotherapy · 2012Article
- Article
- The trypanocidal activity of amidine compounds does not correlate with their binding affinity to Trypanosoma cruzi kinetoplast DNA.Antimicrobial agents and chemotherapy · 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
- Screening of Potential anti-Trypanosoma cruzi Candidates: In Vitro and In Vivo Studies.The open medicinal chemistry journal · 2011Article
- Croton cajucara crude extract and isolated terpenes: activity on Trypanosoma cruzi.Parasitology research · 2010Article
- Arylimidamide DB766, a potential chemotherapeutic candidate for Chagas' disease treatment.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aromatic diamidines represent a class of DNA minor groove-binding ligands that exhibit high levels of antiparasitic activity. Since the chemotherapy for Chagas' disease is still an unsolved problem and previous reports on diamidines and related analogues show that they have high levels of activity against Trypanosoma cruzi infection both in vitro and in vivo, our present aim was to evaluate the cellular effects in vitro of three reversed amidines (DB889, DB702, and DB786) and one diguanidine (DB711) against both amastigotes and bloodstream trypomastigotes of T. cruzi, the etiological agent of Chagas' disease. Our data show that the reversed amidines have higher levels of activity than the diguanidine, with the order of trypanocidal activities being as follows: DB889 > DB702 > DB786 > DB711. Transmission electron microscopy analysis showed that the reversed amidines induced many alterations in the nuclear morphology, swelling of the endoplasmic reticulum and Golgi structures, and consistent damage in the mitochondria and kinetoplasts of the parasites. Interestingly, in trypomastigotes treated with the reversed amidine DB889, multiple axoneme structures (flagellar microtubules) were noted. Flow cytometry analysis confirmed that the treated parasites presented an important loss of the mitochondrial membrane potential, as revealed by a decrease in rhodamine 123 fluorescence. Our results show that the reversed amidines have promising activities against the relevant mammalian forms of T. cruzi and display high trypanocidal effects at very low doses. This is especially the case for DB889, which merits further in vivo evaluation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.