ArticlePloS one2020
Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
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- Ethnobotany, phytochemistry and pharmacological properties of Fagopyri Dibotryis Rhizoma: A review.Frontiers in pharmacology · 2023Review
- Treatment of Human Babesiosis: Then and Now.Pathogens (Basel, Switzerland) · 2021Review
- The First Insight Into the Supramolecular System ofFrontiers in chemistry · 2021Article
- Joining forces: Leveraging novel combination therapies to combat infections with eukaryotic pathogens.PLoS pathogens · 2020Article
- Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection.Antimicrobial agents and chemotherapy · 2020Article
- Factors Associated with Increased Morbidity and Mortality of Obese and Overweight COVID-19 Patients.Biology · 2020Review
- Inhibitory effects of novel ciprofloxacin derivatives on the growth of four Babesia species and Theileria equi.Parasitology research · 2020Article
- Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects.Pharmaceuticals (Basel, Switzerland) · 2020Review
- In vitro and in vivo growth inhibitory activities of cryptolepine hydrate against several Babesia species and Theileria equi.PLoS neglected tropical diseases · 2020Article
- Assessing the Immunochromatographic Test Strip for Serological Detection of Bovine Babesiosis in Uganda.Microorganisms · 2020Article
- Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Wormwood (Antibiotics (Basel, Switzerland) · 2020Review
- Chemical Constituents and Pharmacological Activities of Garlic (Nutrients · 2020Review
- Gas chromatography-mass spectrometry analysis, phytochemical screening and antiprotozoal effects of the methanolic Viola tricolor and acetonic Laurus nobilis extracts.BMC complementary medicine and therapies · 2020Article
- Traditional Uses, Bioactive Chemical Constituents, and Pharmacological and Toxicological Activities ofBiomolecules · 2020Review
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe plenteous resistance to and undesirable consequences of the existing antipiroplasmic therapies have emphasized the urgent need for new chemotherapeutics and drug targets for both prophylaxis and chemotherapy. Hydroxyurea (HYD) is an antineoplastic agent with antitrypanosomal activity. Eflornithine (α-difluoro-methyl ornithine, DFMO) is the best choice therapy for the treatment of late-stage Gambian human African trypanosomiasis.
methodsIn this study, the inhibitory and combination efficacy of HYD and DFMO with existing babesicidal drugs (diminazene aceturate (DA), atovaquone (ATV), and clofazimine (CLF)) deoxyribonucleotide in vitro against the multiplication of Babesia and Theileria. As well as, their chemotherapeutic effects were assessed on B. microti strain that infects rodents. The Cell Counting Kits-8 (CCK-8) test was used to examine their cytotoxicity on human foreskin fibroblast (HFF), mouse embryonic fibroblast (NIH/3T3), and Madin-Darby bovine kidney (MDBK) cells.
findingsHYD and DFMO suppressed the multiplication of all tested species (B. bigemina, B. bovis, B. caballi, B. divergens, and T. equi) in a dose-related manner. HFF, NIH/3T3, or MDBK cell viability was not influenced by DFMO at 1000 μM, while HYD affected the MDBK cell viability at EC50 value of 887.5±14.4 μM. The in vitro combination treatments of DFMO and HYD with CLF, DA, and ATV exhibited synergistic and additive efficacy toward all tested species. The in vivo experiment revealed that HYD and DFMO oral administration at 100 and 50 mg/kg inhibited B. microti multiplication in mice by 60.1% and 78.2%, respectively. HYD-DA and DFMO-DA combined treatments showed higher chemotherapeutic efficacy than their monotherapies.
conclusionThese results indicate the prospects of HYD and DFMO as drug candidates for piroplasmosis treatment, when combined mainly with DA, ATV, and CLF. Therefore, further studies are needed to combine HYD or DFMO with either ATV or CLF and examine their impact on B. microti infection in mice.
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