ArticleAntimicrobial agents and chemotherapy2015
Antileishmanial Activity of Disulfiram and Thiuram Disulfide Analogs in an Ex Vivo Model System Is Selectively Enhanced by the Addition of Divalent Metal Ions.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- In Vivo Trypanocidal Activity of the Drug Disulfiram Combined with Benznidazole.ACS infectious diseases · 2026Article
- The pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use.Parasites & vectors · 2023Review
- Article
- Disulfiram: Mechanisms, Applications, and Challenges.Antibiotics (Basel, Switzerland) · 2023Review
- Antiparasitic Activities of Compounds Isolated fromAntibiotics (Basel, Switzerland) · 2023Article
- Antifungal activity of the repurposed drug disulfiram againstFrontiers in pharmacology · 2023Article
- Disulfiram: A Repurposed Drug in Preclinical and Clinical Development for the Treatment of Infectious Diseases.Anti-infective agents · 2022Article
- Comparative study of the effects of ziram and disulfiram on human monocyte-derived macrophage functions and polarization: involvement of zinc.Cell biology and toxicology · 2021Article
- Drug Repurposing of the Alcohol Abuse Medication Disulfiram as an Anti-Parasitic Agent.Frontiers in cellular and infection microbiology · 2021Article
- Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases.Antibiotics (Basel, Switzerland) · 2019Article
- Discovery of novel, orally bioavailable, antileishmanial compounds using phenotypic screening.PLoS neglected tropical diseases · 2017Article
- Marine Algae as Source of Novel Antileishmanial Drugs: A Review.Marine drugs · 2017Review
- Nanostructured delivery systems with improved leishmanicidal activity: a critical review.International journal of nanomedicine · 2017Review
- Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis.Frontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current treatments for cutaneous and visceral leishmaniasis are toxic, expensive, difficult to administer, and limited in efficacy and availability. Disulfiram has primarily been used to treat alcoholism. More recently, it has shown some efficacy as therapy against protozoan pathogens and certain cancers, suggesting a wide range of biological activities. We used an ex vivo system to screen several thiuram disulfide compounds for antileishmanial activity. We found five compounds (compound identifier [CID] 7188, 5455, 95876, 12892, and 3117 [disulfiram]) with anti-Leishmania activity at nanomolar concentrations. We further evaluated these compounds with the addition of divalent metal salts based on studies that indicated these salts could potentiate the action of disulfiram. In addition, clinical studies suggested that zinc has some efficacy in treating cutaneous leishmaniasis. Several divalent metal salts were evaluated at 1 μM, which is lower than the normal levels of copper and zinc in plasma of healthy individuals. The leishmanicidal activity of disulfiram and CID 7188 were enhanced by several divalent metal salts at 1 μM. The in vitro therapeutic index (IVTI) of disulfiram and CID 7188 increased 12- and 2.3-fold, respectively, against L. major when combined with ZnCl2. The combination of disulfiram with ZnSO4 resulted in a 1.8-fold increase in IVTI against L. donovani. This novel combination of thiuram disulfides and divalent metal ions salts could have application as topical and/or oral therapies for treatment of cutaneous and visceral leishmaniasis.
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