ArticleAntimicrobial agents and chemotherapy2002
Resistance to pentamidine in Leishmania mexicana involves exclusion of the drug from the mitochondrion.
Article in Antimicrobial agents and chemotherapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.Parasitology · 2013Pooled it
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Interventions for Neglected Diseases Caused by Kinetoplastid Parasites: A One Health Approach to Drug Discovery, Development, and Deployment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- Progress in antileishmanial drugs: Mechanisms, challenges, and prospects.PLoS neglected tropical diseases · 2025Review
- Amidine containing compounds: Antimicrobial activity and its potential in combating antimicrobial resistance.Heliyon · 2024Review
- Evaluation of theACS infectious diseases · 2024Article
- ABC transporter inhibition by beauvericin partially overcomes drug resistance inAntimicrobial agents and chemotherapy · 2024Article
- Synthesis and Biophysical and Biological Studies ofJournal of medicinal chemistry · 2023Article
- Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host.Pathogens (Basel, Switzerland) · 2023Review
- Selective Anti-Leishmanial Strathclyde Minor Groove Binders Using an N-Oxide Tail-Group Modification.International journal of molecular sciences · 2022Article
- In vitro effect of artemether-loaded nanostructured lipid carrier (NLC) onJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021Article
- The Phlebotomus papatasi systemic transcriptional response to trypanosomatid-contaminated blood does not differ from the non-infected blood meal.Parasites & vectors · 2021Article
- Nanoparticles Formulations of Artemisinin and Derivatives as Potential Therapeutics for the Treatment of Cancer, Leishmaniasis and Malaria.Pharmaceutics · 2020Review
- Sterol 14-α-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major.PLoS pathogens · 2020Article
- The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History.Tropical medicine and infectious disease · 2020Review
- An Overview of Drug Resistance in Protozoal Diseases.International journal of molecular sciences · 2019Review
- Recent developments in compounds acting in the DNA minor groove.MedChemComm · 2019Review
- Functional and structural analysis of AT-specific minor groove binders that disrupt DNA-protein interactions and cause disintegration of the Trypanosoma brucei kinetoplast.Nucleic acids research · 2017Article
- Organic cation transporter 1 (OCT1) is involved in pentamidine transport at the human and mouse blood-brain barrier (BBB).PloS one · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The uptake of [(3)H]pentamidine into wild-type and drug-resistant strains of Leishmania mexicana was compared. Uptake was carrier mediated. Pentamidine-resistant parasites showed cross-resistance to other toxic diamidine derivatives. A substantial decrease in accumulation of the drug accompanied the resistance phenotype, although the apparent affinity for pentamidine by its carrier was not altered when initial uptake velocity was measured. The apparent V(max), however, was reduced. An efflux of pentamidine could be measured in both wild-type and resistant cells. Only a relatively small proportion of the total accumulated pentamidine was available for efflux in wild-type cells, while in resistant cells the majority of loaded pentamidine was available for release. Pharmacological reagents which diminish the mitochondrial membrane potential reduced pentamidine uptake in wild-type parasites, and the mitochondrial membrane potential was shown to be reduced in resistant cells. A fluorescent analogue of pentamidine, 4',6'-diamidino-2-phenylindole, accumulated in the kinetoplast of wild-type but not resistant parasites. These data together indicate that diamidine drugs accumulate in the Leishmania mitochondrion and that the development of the resistance phenotype is accompanied by lack of mitochondrial accumulation of the drug and its exclusion from the parasites.
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