ArticleMolecules (Basel, Switzerland)2022
Phenotypic Evaluation of Nucleoside Analogues against
Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
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- The impact of probiotic administration in vivo on peritoneal mouse macrophages infected by Leishmania amazonensis ex vivo.Memorias do Instituto Oswaldo Cruz · 2025Article
- Guanine derivatives as promising candidates for the development of purine-based antimalarial drugs.Frontiers in parasitology · 2025Article
- Nucleoside Analogues for Chagas Disease and Leishmaniasis Therapy: Current Status and Future Perspectives.Molecules (Basel, Switzerland) · 2024Review
- Synthesis and Anti-Molecules (Basel, Switzerland) · 2024Article
- Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models.Memorias do Instituto Oswaldo Cruz · 2024Review
- Antitrypanosomal Activity of 1,2,3-Triazole-Based Hybrids Evaluated Using In Vitro Preclinical Translational Models.Biology · 2023Article
- Antiparasitic Activity ofPharmaceutics · 2023Article
- Cloning and Characterization ofInternational journal of molecular sciences · 2023Article
- Pyrimidine salvage inFrontiers in cellular and infection microbiology · 2023Article
- TheMolecules (Basel, Switzerland) · 2022Article
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3′-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 μM, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.
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