ArticlePloS one2014
A quinoxaline derivative as a potent chemotherapeutic agent, alone or in combination with benznidazole, against Trypanosoma cruzi.
Article in PloS one, 2014. 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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Who cites it
17 citing papers in PubMed, 48 citations in OpenAlex.
- Compounds Containing 2,3-Bis(phenylamino) Quinoxaline Exhibit Activity Against Methicillin-Resistant Staphylococcus aureus, Enterococcus faecalis, and Their Biofilms.MicrobiologyOpen · 2024Article
- Piplartine-Inspired 3,4,5-Trimethoxycinnamates: Trypanocidal, Mechanism of Action, and In Silico Evaluation.Molecules (Basel, Switzerland) · 2023Article
- Fexinidazole interferes with the growth and structural organization of Trypanosoma cruzi.Scientific reports · 2022Article
- Miltefosine and Benznidazole Combination Improve Anti-Frontiers in cellular and infection microbiology · 2022Article
- Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives onFrontiers in cellular and infection microbiology · 2022Article
- Optimization and biological validation of anBiology methods & protocols · 2021Article
- Arg-substituted VmCT1 analogs reveals promising candidate for the development of new antichagasic agent.Parasitology · 2020Article
- Biological activity of esters of quinoxaline-7-carboxylate 1,4-di-N-oxide against E. histolytica and their analysis as potential thioredoxin reductase inhibitors.Parasitology research · 2020Article
- Trypanocidal Mechanism of Action andInternational journal of molecular sciences · 2019Article
- NitroketeneRSC advances · 2019Review
- Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment.Memorias do Instituto Oswaldo Cruz · 2018Article
- Digital imaging information technology for biospeckle activity assessment relative to bacteria and parasites.Lasers in medical science · 2017Article
- Effects of (1BioMed research international · 2017Article
- Quantitative Laser Biospeckle Method for the Evaluation of the Activity of Trypanosoma cruzi Using VDRL Plates and Digital Analysis.PLoS neglected tropical diseases · 2016Article
- In Vitro and In Vivo Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis.Antimicrobial agents and chemotherapy · 2016Article
- Dibenzylideneacetones Are Potent Trypanocidal Compounds That Affect the Trypanosoma cruzi Redox System.Antimicrobial agents and chemotherapy · 2016Article
- The Combination of Vitamin K3 and Vitamin C Has Synergic Activity against Forms of Trypanosoma cruzi through a Redox Imbalance Process.PloS one · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChagas' disease is a condition caused by the protozoan Trypanosoma cruzi that affects millions of people, mainly in Latin America where it is considered endemic. The chemotherapy for Chagas disease remains a problem; the standard treatment currently relies on a single drug, benznidazole, which unfortunately induces several side effects and it is not successful in the cure of most of the chronic patients. In order to improve the drug armamentarium against Chagas' disease, in the present study we describe the synthesis of the compound 3-chloro-7-methoxy-2-(methylsulfonyl) quinoxaline (quinoxaline 4) and its activity, alone or in combination with benznidazole, against Trypanosoma cruzi in vitro. METHODOLOGY/PRINCIPAL
findingsQuinoxaline 4 was found to be strongly active against Trypanosoma cruzi Y strain and more effective against the proliferative forms. The cytotoxicity against LLCMK2 cells provided selective indices above one for all of the parasite forms. The drug induced very low hemolysis, but its anti-protozoan activity was partially inhibited when mouse blood was added in the experiment against trypomastigotes, an effect that was specifically related to blood cells. A synergistic effect between quinoxaline 4 and benznidazole was observed against epimastigotes and trypomastigotes, accompanied by an antagonistic interaction against LLCMK2 cells. Quinoxaline 4 induced several ultrastructural alterations, including formations of vesicular bodies, profiles of reticulum endoplasmic surrounding organelles and disorganization of Golgi complex. These alterations were also companied by cell volume reduction and maintenance of cell membrane integrity of treated-parasites. CONCLUSION/SIGNIFICANCE: Our results demonstrated that quinoxaline 4, alone or in combination with benznidazole, has promising effects against all the main forms of T. cruzi. The compound at low concentrations induced several ultrastructural alterations and led the parasite to an autophagic-like cell death. Taken together these results may support the further development of a combination therapy as an alternative more effective in Chagas' disease treatment.
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