ArticleAntimicrobial agents and chemotherapy2015
In Vitro and In Vivo Investigation of the Inhibition of Trypanosoma brucei Cell Growth by Lipophilic Bisphosphonates.
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 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Bisphosphonates synergistically enhance the antifungal activity of azoles in dermatophytes and other pathogenic molds.mSphere · 2024Article
- Spectrum of activity and mechanisms of azole-bisphosphonate synergy in pathogenicMicrobiology spectrum · 2024Article
- Developmental Transcriptome Analysis of Red-Spotted Apollo Butterfly,International journal of molecular sciences · 2022Article
- Article
- Identifying Structural Determinants of Product Specificity inBiochemistry · 2020Article
- Bisphosphonate-Based Molecules as Potential New Antiparasitic Drugs.Molecules (Basel, Switzerland) · 2020Review
- Phosphonate and Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthases: A Structure-Guided Perspective.Frontiers in chemistry · 2020Review
- Novel lead compounds in pre-clinical development against African sleeping sickness.MedChemComm · 2017Review
- Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions.PLoS neglected tropical diseases · 2017Article
- Antileishmanial Mechanism of Diamidines Involves Targeting Kinetoplasts.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
We report the results of a screen of a library of 925 potential prenyl synthase inhibitors against Trypanosoma brucei farnesyl diphosphate synthase (TbFPPS) and against T. brucei, the causative agent of human African trypanosomiasis. The most potent compounds were lipophilic analogs of the bone resorption drug zoledronate, some of which had submicromolar to low micromolar activity against bloodstream form T. brucei and selectivity indices of up to ∼ 300. We evaluated the effects of two such inhibitors on survival and parasitemia in a T. brucei mouse model of infection and found that survival increased by up to 16 days. We also investigated the binding of three lipophilic bisphosphonates to an expressed TbFPPS using crystallography and investigated the thermodynamics of binding using isothermal titration calorimetry.
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Registered trials
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.