ArticleScientific reports2018
Identifying inhibitors of the Leishmania inositol phosphorylceramide synthase with antiprotozoal activity using a yeast-based assay and ultra-high throughput screening platform.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- An experimental target-based platform in yeast for screening Plasmodium vivax deoxyhypusine synthase inhibitors.PLoS neglected tropical diseases · 2024Article
- Evaluation of theACS infectious diseases · 2024Article
- Identification of potential inhibitor against Leishmania donovani mitochondrial DNA primase through in-silico and in vitro drug repurposing approaches.Scientific reports · 2024Article
- Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity.PLoS neglected tropical diseases · 2023Article
- Genome deletions to overcome the directed loss of gene function inFrontiers in cellular and infection microbiology · 2022Article
- Challenges and Tools for In VitroPathogens (Basel, Switzerland) · 2021Review
- Pyrrolidine-based 3-deoxysphingosylphosphorylcholine analogs as possible candidates against neglected tropical diseases (NTDs): identification of hit compounds towards development of potential treatment ofJournal of enzyme inhibition and medicinal chemistry · 2021Article
- Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of theACS infectious diseases · 2021Article
- An Overview on the Therapeutics of Neglected Infectious Diseases-Leishmaniasis and Chagas Diseases.Frontiers in chemistry · 2021Review
- An investigation of the antileishmanial properties of semi-synthetic saponins.RSC medicinal chemistry · 2020Article
- Mining for natural product antileishmanials in a fungal extract library.International journal for parasitology. Drugs and drug resistance · 2019Article
- A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.Cellular signalling · 2019Article
- The identification of small molecule inhibitors of the plant inositol phosphorylceramide synthase which demonstrate herbicidal activity.Scientific reports · 2019Article
- Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania.International journal for parasitology. Drugs and drug resistance · 2018Article
- Article
- Development of NanoLuc-PEST expressing Leishmania mexicana as a new drug discovery tool for axenic- and intramacrophage-based assays.PLoS neglected tropical diseases · 2018Article
- Microfluidic Devices for Drug Assays.High-throughput · 2018Review
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12 authors.
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Abstract
Leishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the world's poorest, however vaccines are absent and drug therapy limited. Recently, public-private partnerships have developed to identify new modes of controlling leishmaniasis. Drug discovery is a significant part of these efforts and here we describe the development and utilization of a novel assay to identify antiprotozoal inhibitors of the Leishmania enzyme, inositol phosphorylceramide (IPC) synthase. IPC synthase is a membrane-bound protein with multiple transmembrane domains, meaning that a conventional in vitro assay using purified protein in solution is highly challenging. Therefore, we utilized Saccharomyces cerevisiae as a vehicle to facilitate ultra-high throughput screening of 1.8 million compounds. Antileishmanial benzazepanes were identified and shown to inhibit the enzyme at nanomolar concentrations. Further chemistry produced a benzazepane that demonstrated potent and specific inhibition of IPC synthase in the Leishmania cell.
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