Abstract:
:The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036-0.12; 95% CI] or 21.9 ng/ml [12.1-40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection.
journal_name
Int J Parasitol Drugs Drug Resistauthors
Bowden GD,Land KM,O'Connor RM,Fritz HMdoi
10.1016/j.ijpddr.2018.02.002subject
Has Abstractpub_date
2018-04-01 00:00:00pages
137-144issue
1issn
2211-3207pii
S2211-3207(17)30132-Xjournal_volume
8pub_type
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journal_title:International journal for parasitology. Drugs and drug resistance
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abstract::Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vi...
journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
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abstract::Soil-transmitted helminths cause more than 1 billion human infections globally, mostly in the poorest regions of the world. Control relies essentially on a limited panel of four drugs, and drug resistance might be inescapable. Nitazoxanide, an anti-infective drug, has been shown to exert anthelmintic activity in human...
journal_title:International journal for parasitology. Drugs and drug resistance
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doi:10.1016/j.ijpddr.2012.02.004
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abstract::The high level of resistance to the macrocyclic lactones has encouraged the search for strategies to optimize their potential as antiparasitic agents. There is a need for pharmaco-parasitological studies addressing the kinetic-dynamic differences between various macrocyclic lactones under standardized in vivo conditio...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2012.11.001
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abstract::The four components present in the trypanocidal treatment Samorin, the commercially available formulation of isometamidium, were separated and purified by column chromatography. These compounds as well as the Samorin mixture and the other phenanthridine trypanocide, homidium, were tested on Trypanosoma congolense and ...
journal_title:International journal for parasitology. Drugs and drug resistance
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doi:10.1016/j.ijpddr.2019.01.003
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abstract::Cryptosporidium and Toxoplasma are parasites that have caused problems worldwide. Cryptosporidium causes severe watery diarrhoea and may be fatal in immunocompromised patients and in infants. Nitazoxanide is the only agent currently approved by the FDA, but its efficacy is limited. Toxoplasmosis is also a problem in t...
journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.01.001
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.11.004
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abstract::Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been doc...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.10.002
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abstract::Toxicity and poor adherence to treatment that favors the generation of resistance in the Leishmania parasites highlight the need to develop better alternatives. Here, we evaluated the in vitro effectiveness of hydrazone derived from chromanes 2-(2,3-dihydro-4H-1-benzothiopyran-4-ylidene) hydrazide (TC1) and 2-(2,3-dih...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.06.004
更新日期:2020-08-01 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.08.006
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章,评审
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更新日期:2011-10-14 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.11.001
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.09.006
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.12.005
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2017.10.002
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.04.001
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.02.004
更新日期:2018-04-01 00:00:00
abstract::The need for new antimalarials is persistent due to the emergence of drug resistant parasites. Here we aim to identify new drug targets in Plasmodium falciparum by phylogenomics among the Plasmodium spp. and comparative genomics to Homo sapiens. The proposed target discovery pipeline is largely independent of experime...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2012.07.002
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journal_title:International journal for parasitology. Drugs and drug resistance
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doi:10.1016/j.ijpddr.2016.06.004
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2013.04.002
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.11.003
更新日期:2018-12-01 00:00:00
abstract::Neglected tropical diseases are of growing worldwide concern and schistosomiasis, caused by parasitic flatworms, continues to be a major threat with more than 200 million people requiring preventive treatment. As praziquantel (PZQ) remains the treatment of choice, an urgent need for alternative treatments motivates re...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.05.002
更新日期:2020-08-01 00:00:00
abstract::The effect of Camellia sinensis (green tea) on the growth of Acanthamoeba castellanii trophozoites was examined using a microplate based-Sulforhodamine B (SRB) assay. C. sinensis hot and cold brews at 75% and 100% concentrations significantly inhibited the growth of trophozoites. We also examined the structural altera...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.05.001
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abstract::Nematode cys-loop ligand-gated ion channels (LGICs) have been shown to be attractive targets for the development of novel anti-parasitic drugs. The ACC-1 family of receptors are a unique group of acetylcholine-gated chloride channels present only in invertebrates, and sequence analysis suggests that they contain a nov...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.09.004
更新日期:2018-12-01 00:00:00
abstract::Macrocyclic lactone (ML) anthelmintics are the most important class of anthelmintics because of our high dependence on them for the control of nematode parasites and some ectoparasites in livestock, companion animals and in humans. However, resistance to MLs is of increasing concern. Resistance is commonplace througho...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章,评审
doi:10.1016/j.ijpddr.2019.06.002
更新日期:2019-08-01 00:00:00
abstract::It is recognized that the clinical efficacy of single dose benzimidazoles (BZs) against the nematode, Trichuris suis of pigs and the closely related Trichuris trichiura in humans is only poor to moderate. Recent in vitro studies have indicated that a low uptake of fenbendazole (FBZ) in T. suis may be responsible for i...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.03.003
更新日期:2014-04-08 00:00:00