ArticleAntimicrobial agents and chemotherapy2011
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
Article in Antimicrobial agents and chemotherapy, 2011. 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, 35 citations in OpenAlex.
- 4-Aminoquinoline as a privileged scaffold for the design of leishmanicidal agents: structure-property relationships and key biological targets.Frontiers in chemistry · 2024Review
- Mitochondrial Imbalance ofACS omega · 2022Article
- The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates.Molecules (Basel, Switzerland) · 2022Review
- Sterol 14-α-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major.PLoS pathogens · 2020Article
- Article
- A semi-synthetic neolignan derivative from dihydrodieugenol B selectively affects the bioenergetic system of Leishmania infantum and inhibits cell division.Scientific reports · 2019Article
- Molecular Basis of the Leishmanicidal Activity of the Antidepressant Sertraline as a Drug Repurposing Candidate.Antimicrobial agents and chemotherapy · 2018Article
- The mitochondrial SIR2 related protein 2 (SIR2RP2) impacts Leishmania donovani growth and infectivity.PLoS neglected tropical diseases · 2017Article
- Allicin Induces Calcium and Mitochondrial Dysregulation Causing Necrotic Death in Leishmania.PLoS neglected tropical diseases · 2016Article
- The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.Antimicrobial agents and chemotherapy · 2015Article
- Identification of metal dithiocarbamates as a novel class of antileishmanial agents.Antimicrobial agents and chemotherapy · 2015Article
- A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum.PloS one · 2015Article
- Idiosyncratic quinoline central nervous system toxicity: Historical insights into the chronic neurological sequelae of mefloquine.International journal for parasitology. Drugs and drug resistance · 2014Article
- 4-amino bis-pyridinium derivatives as novel antileishmanial agents.Antimicrobial agents and chemotherapy · 2014Article
- A new ABC half-transporter in Leishmania major is involved in resistance to antimony.Antimicrobial agents and chemotherapy · 2013Article
- Metabolic network analysis predicts efficacy of FDA-approved drugs targeting the causative agent of a neglected tropical disease.BMC systems biology · 2012Article
- Leishmania donovani develops resistance to drug combinations.PLoS neglected tropical diseases · 2012Article
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
Tafenoquine (TFQ), an 8-aminoquinoline used to treat and prevent Plasmodium infections, could represent an alternative therapy for leishmaniasis. Indeed, TFQ has shown significant leishmanicidal activity both in vitro and in vivo, where it targets Leishmania mitochondria and activates a final apoptosis-like process. In order not to jeopardize the life span of this potential antileishmania drug, it is important to determine the likelihood that Leishmania will develop resistance to TFQ and the mechanisms of resistance induced. To address this issue, a TFQ-resistant Leishmania major promastigote line (R4) was selected. This resistance, which is unstable in a drug-free medium (revertant line), was maintained in intramacrophage amastigote forms, and R4 promastigotes were found to be cross-resistant to other 8-aminoquinolines. A decreased TFQ uptake, which is probably associated with an alkalinization of the intracellular pH rather than drug efflux, was observed for both the R4 and revertant lines. TFQ induces a decrease in ATP synthesis in all Leishmania lines, although total ATP levels were maintained at higher values in R4 parasites. In contrast, ATP synthesis by glycolysis was significantly increased in R4 parasites, whereas mitochondrial ATP synthesis was similar to that in wild-type parasites. We therefore conclude that increased glycolytic ATP synthesis is the main mechanism underlying TFQ resistance in Leishmania.
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