ArticleAntimicrobial agents and chemotherapy2014
Disuccinyl betulin triggers metacaspase-dependent endonuclease G-mediated cell death in unicellular protozoan parasite Leishmania donovani.
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 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Antileishmanial Activity of Bioactive Compounds Obtained fromMolecules (Basel, Switzerland) · 2026Pooled it
- Dissecting The role ofEmerging microbes & infections · 2022Article
- Biodegradable and Bioactive Carriers Based on Poly(betulin disuccinate-Pharmaceutics · 2022Article
- Leishmanicidal Activity of Betulin Derivatives inMicroorganisms · 2021Article
- Bioactive Betulin and PEG Based Polyanhydrides for Use in Drug Delivery Systems.International journal of molecular sciences · 2021Article
- Novel polymeric derivatives of betulin with anticancer activity.RSC advances · 2019Article
- Cell death in Leishmania.Parasite (Paris, France) · 2019Review
- Metacaspases: Potential Drug Target Against Protozoan Parasites.Frontiers in pharmacology · 2019Review
- Cinnamaldehyde, a Promising Natural Preservative AgainstFrontiers in microbiology · 2019Article
- Ammonium trichloro [1,2-ethanediolato-O,O']-tellurate cures experimental visceral leishmaniasis by redox modulation of Leishmania donovani trypanothione reductase and inhibiting host integrin linked PI3K/Akt pathway.Cellular and molecular life sciences : CMLS · 2018Article
- Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani.Scientific reports · 2017Article
- Induction of Early Autophagic Process onFrontiers in microbiology · 2017Article
- A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both In Vitro and In Vivo by Targeting Type IB Topoisomerase.Antimicrobial agents and chemotherapy · 2016Article
- Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal CaMicrobial cell (Graz, Austria) · 2015Article
- Green Synthesis of Silver and Titanium Dioxide Nanoparticles Using Euphorbia prostrata Extract Shows Shift from Apoptosis to G0/G1 Arrest followed by Necrotic Cell Death in Leishmania donovani.Antimicrobial agents and chemotherapy · 2015Article
- Die for the community: an overview of programmed cell death in bacteria.Cell death & disease · 2015Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unicellular organism Leishmania undergoes apoptosis-like cell death in response to external stress or exposure to antileishmanial agents. Here, we showed that 3-O,28-O-disuccinyl betulin (DiSB), a potent topoisomerase type IB inhibitor, induced parasitic cell death by generating oxidative stress. The characteristic feature of the death process resembled the programmed cell death (PCD) seen in higher eukaryotes. In the current study, the generation of reactive oxygen species (ROS), followed by the depolarization of mitochondrial membrane potential (ΔΨm), caused a loss in ATP production in Leishmania parasites. This further gave positive feedback to produce a large amount of ROS, which in turn caused oxidative DNA lesions and genomic DNA fragmentation. The treatment of promastigotes with DiSB induced high expression levels of metacaspase protein that led to cell death in this unicellular organism. The PCD was insensitive to benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), suggesting that the death process was not associated with the activation of caspases. DiSB treatment translocated Leishmania donovani endonuclease G (LdEndoG) from mitochondria to the nucleus, which was responsible for the DNA degradation process. Conditional antisense knockdown of L. donovani metacaspase (LdMC), as well as EndoG, -subverted death of the parasite and rescued cell cycle arrest in G1 phase. The present study on the effector molecules associated with the PCD pathway of the parasite should help to manifest the mechanisms of PCD and also might be exploited in antileishmanial chemotherapy.
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