ArticleAntimicrobial agents and chemotherapy2013
A novel Leishmania major amastigote assay in 96-well format for rapid drug screening and its use for discovery and evaluation of a new class of leishmanicidal quinolinium salts.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Evolution of the Quinoline Scaffold for the Treatment of Leishmaniasis: A Structural Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Macrophage variants in laboratory research: most are well done, but some are RAW.Frontiers in cellular and infection microbiology · 2024Review
- Challenges and Tools for In VitroPathogens (Basel, Switzerland) · 2021Review
- An Antiparasitic Compound from the Medicines for Malaria Venture Pathogen Box PromotesACS infectious diseases · 2020Article
- Essential roles for deubiquitination in Leishmania life cycle progression.PLoS pathogens · 2020Article
- Infectivity and Drug Susceptibility Profiling of DifferentPathogens (Basel, Switzerland) · 2020Article
- Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites.Journal of visualized experiments : JoVE · 2018Article
- Development of a New Antileishmanial Aziridine-2,3-Dicarboxylate-Based Inhibitor with High Selectivity for Parasite Cysteine Proteases.Antimicrobial agents and chemotherapy · 2016Article
- Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210.Parasites & vectors · 2015Article
- Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl and Thymyl Cinnamate Induce Cytoplasmic Vacuoles and Death in Schistosomula of Schistosoma mansoni.Molecules (Basel, Switzerland) · 2015Article
- Antileishmanial and cytotoxic compounds from Valeriana wallichii and identification of a novel nepetolactone derivative.Molecules (Basel, Switzerland) · 2015Article
- Species-specific antimonial sensitivity in Leishmania is driven by post-transcriptional regulation of AQP1.PLoS neglected tropical diseases · 2015Article
- Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB).PLoS neglected tropical diseases · 2015Article
- Development, characterization, and in vitro biological performance of fluconazole-loaded microemulsions for the topical treatment of cutaneous leishmaniasis.BioMed research international · 2015Article
- Article
- Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.PLoS neglected tropical diseases · 2014Article
- 4-amino bis-pyridinium derivatives as novel antileishmanial agents.Antimicrobial agents and chemotherapy · 2014Article
- INsPECT, an open-source and versatile software for automated quantification of (Leishmania) intracellular parasites.PLoS neglected tropical diseases · 2014Article
- Antileishmanial lead structures from nature: analysis of structure-activity relationships of a compound library derived from caffeic Acid bornyl ester.Molecules (Basel, Switzerland) · 2014Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In most laboratories, the screening for leishmanicidal compounds is carried out with Leishmania promastigotes or axenic amastigotes. However, the best approach to identify leishmanicidal compounds is the use of amastigotes residing in macrophages. Reporter gene-based assays are relatively new tools in the search for drugs against eucaryotic protozoa, permitting the development of faster, more automated assays. In this paper, we report on the establishment of a rapid screening assay in a 96-well format. A luciferase-transgenic (Luc-tg) Leishmania major strain was generated and used to infect bone marrow-derived macrophages (BMDM). Amastigote-infected BMDM were treated with different compound concentrations. Cells were lysed with a luciferin-containing buffer, and the resulting luminescence was measured to determine the half-maximal inhibitory concentration (IC50). To validate this new amastigote screening assay, a library of a new class of quinolinium salts was synthesized and tested for leishmanicidal activity. Some of the quinolinium salts showed very promising activities, with IC50s against intracellular amastigotes (IC50 < 1 μg/ml) and selectivity indices (SI > 20) that match the criteria of World Health Organization (WHO) for hits. Compound 21c (IC50 = 0.03 μg/ml; SI = 358) could become a new lead structure for the development of improved chemotherapeutic drugs against L. major. In summary, we describe the establishment of a new 96-well format assay with Luc-transgenic L. major for the rapid screening of compounds for leishmanicidal activity against intracellular amastigotes and its application to the identification of a new class of quinolinium salts with most promising leishmanicidal activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.