ArticleAntimicrobial agents and chemotherapy2013
Characterization of potential drug targets farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase in Schistosoma mansoni.
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 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- An efficient nanocatalytic synthesis of a triazolopyrimidine carbonitrile with potent activity against Trichinella spiralis.Die Naturwissenschaften · 2026Article
- Article
- Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis.PLoS neglected tropical diseases · 2020Article
- Bisphosphonic acids and related compounds as inhibitors of nucleotide- and polyphosphate-processing enzymes: A PPK1 and PPK2 case study.Chemical biology & drug design · 2019Article
- Isoprenoid Biosynthesis Inhibitors Targeting Bacterial Cell Growth.ChemMedChem · 2016Article
- Cloning and characterization of farnesyl pyrophosphate synthase from the highly branched isoprenoid producing diatom Rhizosolenia setigera.Scientific reports · 2015Article
- Natural products as leads in schistosome drug discovery.Molecules (Basel, Switzerland) · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Schistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here that Schistosoma mansoni farnesyl diphosphate synthase (SmFPPS) and geranylgeranyl diphosphate synthase (SmGGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinant SmFPPS and SmGGPPS for subsequent kinetic characterization and testing against a variety of bisphosphonate inhibitors. Recombinant SmFPPS was found to be a soluble 44.2-kDa protein, while SmGGPPS was a soluble 38.3-kDa protein. Characterization of the substrate utilization of the two enzymes indicates that they have overlapping substrate specificities. Against SmFPPS, several bisphosphonates had 50% inhibitory concentrations (IC50s) in the low micromolar to nanomolar range; these inhibitors had significantly less activity against SmGGPPS. Several lipophilic bisphosphonates were active against ex vivo adult worms, with worm death occurring over 4 to 6 days. These results indicate that FPPS and GGPPS could be of interest in the context of the emerging resistance to praziquantel in schistosomiasis therapy.
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Registered trials
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