ArticlePLoS neglected tropical diseases2009
Identification of potent chemotypes targeting Leishmania major using a high-throughput, low-stringency, computationally enhanced, small molecule screen.
Article in PLoS neglected tropical diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review of Curcumin and its Derivatives as Valuable Sources of Antileishmanial Agents.Acta parasitologica · 2021Pooled it
- Potential efficacy of repurposed drugs for treating drug-resistant visceral leishmaniasis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Reclaiming the Microbial Battlefield: Adjuvant Strategies to Overcome Antibiotic Resistance.Microorganisms · 2026Review
- PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds.Journal of parasitology research · 2025Article
- Synthesis and biological evaluation of 4,7,9-trisubstituted benzoxazepines as antileishmanial agents.Bioorganic & medicinal chemistry letters · 2024Article
- Discovery and Optimization of Tambjamines as a Novel Class of Antileishmanial Agents.Journal of medicinal chemistry · 2024Article
- In Vitro Activities of Dithiocarbamate Derivatives againstTropical medicine and infectious disease · 2023Article
- Optimization of Orally Bioavailable Antileishmanial 2,4,5-Trisubstituted Benzamides.Journal of medicinal chemistry · 2023Article
- Disulfiram: Mechanisms, Applications, and Challenges.Antibiotics (Basel, Switzerland) · 2023Review
- Disulfiram: A Repurposed Drug in Preclinical and Clinical Development for the Treatment of Infectious Diseases.Anti-infective agents · 2022Article
- Past and future of trypanosomatids high-throughput phenotypic screening.Memorias do Instituto Oswaldo Cruz · 2022Article
- Chitosan-Based Nanomaterials as Valuable Sources of Anti-Leishmanial Agents: A Systematic Review.Nanomaterials (Basel, Switzerland) · 2021Review
- Development of an automated image analysis protocol for quantification of intracellular forms of Leishmania spp.PloS one · 2018Article
- Discovery of novel, orally bioavailable, antileishmanial compounds using phenotypic screening.PLoS neglected tropical diseases · 2017Article
- Antiparasitic lethality of sulfonamidebenzamides in kinetoplastids.Bioorganic & medicinal chemistry letters · 2017Article
- Imaging flow cytometry analysis of intracellular pathogens.Methods (San Diego, Calif.) · 2017Review
- Calcium Ionophore, Calcimycin, KillsBioMed research international · 2017Article
- Arginine and Polyamines Fate inFrontiers in microbiology · 2017Review
- DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis.Scientific reports · 2016Article
- Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin Resistance in Leishmania major.PLoS neglected tropical diseases · 2016Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Patients with clinical manifestations of leishmaniasis, including cutaneous leishmaniasis, have limited treatment options, and existing therapies frequently have significant untoward liabilities. Rapid expansion in the diversity of available cutaneous leishmanicidal chemotypes is the initial step in finding alternative efficacious treatments. To this end, we combined a low-stringency Leishmania major promastigote growth inhibition assay with a structural computational filtering algorithm. After a rigorous assay validation process, we interrogated approximately 200,000 unique compounds for L. major promastigote growth inhibition. Using iterative computational filtering of the compounds exhibiting > 50% inhibition, we identified 553 structural clusters and 640 compound singletons. Secondary confirmation assays yielded 93 compounds with EC(50)s < or = 1 microM, with none of the identified chemotypes being structurally similar to known leishmanicidals and most having favorable in silico predicted bioavailability characteristics. The leishmanicidal activity of a representative subset of 15 chemotypes was confirmed in two independent assay formats, and L. major parasite specificity was demonstrated by assaying against a panel of human cell lines. Thirteen chemotypes inhibited the growth of a L. major axenic amastigote-like population. Murine in vivo efficacy studies using one of the new chemotypes document inhibition of footpad lesion development. These results authenticate that low stringency, large-scale compound screening combined with computational structure filtering can rapidly expand the chemotypes targeting in vitro and in vivo Leishmania growth and viability.
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Registered trials
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