2016
DOI: 10.1186/s13567-016-0317-1
|View full text |Cite
|
Sign up to set email alerts
|

Repurposing of antiparasitic drugs: the hydroxy-naphthoquinone buparvaquone inhibits vertical transmission in the pregnant neosporosis mouse model

Abstract: The three anti-malarial drugs artemiside, artemisone, and mefloquine, and the naphthoquinone buparvaquone known to be active against theileriosis in cattle and Leishmania infections in rodents, were assessed for activity against Neospora caninum infection. All four compounds inhibited the proliferation of N. caninum tachyzoites in vitro with IC50 in the sub-micromolar range, but artemisone and buparvaquone were most effective (IC50 = 3 and 4.9 nM, respectively). However, in a neosporosis mouse model for cerebr… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

0
27
0

Year Published

2016
2016
2024
2024

Publication Types

Select...
6
3

Relationship

3
6

Authors

Journals

citations
Cited by 33 publications
(27 citation statements)
references
References 40 publications
0
27
0
Order By: Relevance
“…For instance, low nanomolar concentrations of the naphtoquinone buparvaquone inhibited N. caninum proliferation in vitro at concentrations similar to ruthenium complexes, and buparvaquone also impaired vertical transmission in the pregnant neosporosis mouse model, but did not affect CNS infection in dams. 13 Another interesting class are endochin-like quinolones (ELQs), which target the cytochrome bc 1 complex of the mitochondrial electron transport chain in protozoan parasites. 65 Cytochrome bc 1 facilitates the transfer of electrons from ubiquinol to cytochrome c and contains both oxidative (Q o ) sites and reductive (Q i ) catalytic sites.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…For instance, low nanomolar concentrations of the naphtoquinone buparvaquone inhibited N. caninum proliferation in vitro at concentrations similar to ruthenium complexes, and buparvaquone also impaired vertical transmission in the pregnant neosporosis mouse model, but did not affect CNS infection in dams. 13 Another interesting class are endochin-like quinolones (ELQs), which target the cytochrome bc 1 complex of the mitochondrial electron transport chain in protozoan parasites. 65 Cytochrome bc 1 facilitates the transfer of electrons from ubiquinol to cytochrome c and contains both oxidative (Q o ) sites and reductive (Q i ) catalytic sites.…”
Section: Discussionmentioning
confidence: 99%
“…6 While novel drugs have been developed against the classical neglected diseases such as malaria, 7 trypanosomiasis [8][9][10] and leishmaniasis, 11,12 novel options for the treatment of protozoan diseases that affect farm animals are largely missing. 13 Due to the intrinsic similarities between parasites and cancer cells, a reasonable starting point for the discovery of novel anti-parasitic drug candidates is to examine compounds that are being developed against cancer. While metalbased drugs are well-established as anti-cancer agents, 14,15 the currently used drugs against protozoan parasites are organic compounds, and do not contain any metal atoms.…”
Section: Introductionmentioning
confidence: 99%
“…In another in vivo experiment, parasite burden in the brains of male BALB/c mice after treatment by artemisone is lower than that by placebo, mefloquine, or artemiside treatment, suggesting possible efficacy of this drug; however the parasite burden in the lungs after artemisone treatment is higher than those of the above-mentioned drugs [73]. Thus, further in vivo investigations are needed for these drugs.…”
Section: Art and Its Derivatives On N Caninum And E Tenellamentioning
confidence: 99%
“…Since buparvaquone affects the viability of the intracellular schizont already after 2 hours of treatment [49], it is, however, unlikely that this prolyl-isomerase represents the primary target. More recently, buparvaquone was demonstrated to exhibit outstanding activity against N. caninum tachyzoites in vitro [50] and in a pregnant neosporosis mouse model [51]. Since both targets are present in the mammalian host cell as well, it is unclear why apicomplexans such as T. annulata or N. caninum are highly susceptible without any discernible host cell toxicity.…”
Section: Targets Identified Through Whole Organism Screening-basedmentioning
confidence: 99%