ArticleInternational journal for parasitology. Drugs and drug resistance2016
Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis.
Article in International journal for parasitology. Drugs and drug resistance, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
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- Low doses of 3-phenyl-lawsone or meglumine antimoniate delivery by tattooing route are successful in reducing parasite load in cutaneous lesions ofFrontiers in cellular and infection microbiology · 2023Article
- Evaluation of the In Vitro Antiparasitic Effect of the Essential Oil ofMolecules (Basel, Switzerland) · 2022Article
- The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.Frontiers in cellular and infection microbiology · 2022Article
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- Liposomes Composed by Membrane Lipid Extracts from Macrophage Cell Line as a Delivery of the TrypanocidalMaterials (Basel, Switzerland) · 2020Article
- β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2020Article
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- Autophagy in the control and pathogenesis of parasitic infections.Cell & bioscience · 2020Review
- In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, anFrontiers in pharmacology · 2020Article
- Autophagy: A necessary process during theVirulence · 2019Review
- Cell death pathways in pathogenic trypanosomatids: lessons of (over)kill.Cell death & disease · 2019Review
- Microtiter Screening Reveals Oxygen-Dependent Antimicrobial Activity of Natural Products Against Mastitis-Causing Bacteria.Frontiers in microbiology · 2019Article
- Redox Balance Keepers and Possible Cell Functions Managed by Redox Homeostasis inFrontiers in cellular and infection microbiology · 2019Review
- TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosomacruzi.Molecules (Basel, Switzerland) · 2018Article
- The regulation of autophagy differentially affects Trypanosoma cruzi metacyclogenesis.PLoS neglected tropical diseases · 2017Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T. cruzi morphology and surface topography. General plasma membrane waving and blebbing particularly on the cytostome region were observed in the R72-treated parasites. Transmission electron microscopy observations confirmed the surface damage at the cytostome opening vicinity. We also observed ultrastructural evidence of the autophagic mechanism termed macroautophagy. Some of the autophagosomes involved large portions of the parasite cytoplasm and their fusion/confluence may lead to necrotic parasite death. The remarkably enhanced frequency of autophagy triggering was confirmed by quantitating monodansylcadaverine labeling. Some cells displayed evidence of chromatin pycnosis and nuclear fragmentation were detected. This latter phenomenon was also indicated by DAPI staining of R72-treated cells. The apoptotis induction was suggested to take place in circa one-third of the parasites assessed by annexin V labeling measured by flow cytometry. TUNEL staining corroborated the apoptosis induction. Propidium iodide labeling indicate that at least 10% of the R72-treated parasites suffered necrosis within 24 h. The present data indicate that the β-lapachone derivative R72 selectively triggers T. cruzi cell death, involving both apoptosis and autophagy-induced necrosis.
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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.