ArticleInternational journal for parasitology. Drugs and drug resistance2012
Di-cationic arylimidamides act against Neospora caninum tachyzoites by interference in membrane structure and nucleolar integrity and are active against challenge infection in mice.
Article in International journal for parasitology. Drugs and drug resistance, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.Parasitology · 2013Pooled it
- Vaccine-Linked Chemotherapy Approach: Additive Effects of Combining theFrontiers in veterinary science · 2022Article
- Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo.International journal for parasitology. Drugs and drug resistance · 2021Article
- NcPuf1 Is a Key Virulence Factor inPathogens (Basel, Switzerland) · 2020Article
- Endochin-Like Quinolones Exhibit Promising Efficacy AgainstFrontiers in veterinary science · 2018Article
- Treatment of Toxoplasmosis and Neosporosis in Farm Ruminants: State of Knowledge and Future Trends.Current topics in medicinal chemistry · 2018Review
- Two Novel Calcium-Dependent Protein Kinase 1 Inhibitors Interfere with Vertical Transmission in Mice Infected with Neospora caninum Tachyzoites.Antimicrobial agents and chemotherapy · 2017Article
- Drug target identification in protozoan parasites.Expert opinion on drug discovery · 2016Review
- In Vitro and In Vivo Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum.Antimicrobial agents and chemotherapy · 2015Article
- Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens.Antimicrobial agents and chemotherapy · 2015Article
- Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice.International journal for parasitology. Drugs and drug resistance · 2015Article
- A quantitative reverse-transcriptase PCR assay for the assessment of drug activities against intracellular Theileria annulata schizonts.International journal for parasitology. Drugs and drug resistance · 2014Article
- Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.PloS one · 2014Article
- In vitro effects of novel ruthenium complexes in Neospora caninum and Toxoplasma gondii tachyzoites.Antimicrobial agents and chemotherapy · 2013Article
- In vitro and in vivo activities of dicationic diguanidino compounds against Echinococcus multilocularis metacestodes.Antimicrobial agents and chemotherapy · 2013Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neospora caninum is considered to be the main cause of bovine abortion in Europe and the USA, leading to considerable financial impact. Losses are caused directly by abortions or indirectly through breeding of calves with impaired viability. Due to the lack of effective chemotherapy against bovine neosporosis, there is a need to develop new anti-protozoal compounds, which would either eliminate the parasite or avoid its transmission. In order to identify compounds of interest, the in vitro activities of 41 di-cationic pentamidine derivatives were studied employing a transgenic N. caninum clone expressing beta-galactosidase as a reporter gene. The arylimidamide DB745, previously shown to be highly active against Leishmania donovani in vitro and in vivo, appeared as the most promising compound, with an IC50 of 80 nM in 3-day growth assays and severely affecting both host cell invasion as well as intracellular proliferation. TEM of intracellular tachyzoites identified distinct alterations related to the nucleolus and the nuclear and cellular membrane. Long-term growth assays showed that DB745 acted parasiticidal upon the Nc-Liv isolate, but not against the Nc-1 isolate of N. caninum. In vivo studies in N. caninum (Nc-1 isolate) infected mice showed that daily intraperitoneal application of DB745 for a period of 14 days resulted in a decreased number of clinically affected animals, and lower cerebral parasite burdens in DB745-treated mice compared to non-treated mice. These results illustrate the potential of dicationic arylimidamides for the treatment of N. caninum infections.
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Registered trials
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