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In vitro growth inhibition of Theileria equi by bumped kinase inhibitors
- Source :
- Veterinary Parasitology. 251:90-94
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Introduction Theileria equi, an etiologic agent of equine piroplasmosis, is a tick-transmitted hemoprotozoan of the phylum Apicomplexa. Recent outbreaks of piroplasmosis in the United States have renewed interest in safe and effective treatment options. Although imidocarb dipropionate (IMD) is the drug of choice for clearance of T. equi, adverse reactions and recently documented resistance support the need for alternative therapeutic strategies. The recently described bumped kinase inhibitors (BKIs) are a new class of compounds that could potentially be used as safe and effective alternatives to IMD. In an initial effort to evaluate this potential, herein we determined the T. equi growth inhibitory activity of 11 BKIs relative to that of IMD and the previously tested BKI 1294. Because some BKIs have known human ether-a-go-go related gene (hERG) channel activity, we also assessed the hERG activity of each compound with the goal to identify those with the highest potency against T. equi coupled with the lowest potential for cardiotoxicity. Results Six BKIs inhibited T. equi growth in vitro, including the previously evaluated BKI 1294 which was used as a positive control. All six compounds were significantly less potent (higher 50% effective concentration (EC50)) than IMD. Two of those compounds were more potent than BKI 1294 control but had similar hERG activity. Although the remaining three compounds had similar to lower potency than BKI 1294, hERG EC50 was higher for three of them (BKI 1735, BKI 1369 and BKI 1318). Conclusions The BKI compounds evaluated in this study inhibited T. equi in vitro and had diverse hERG activity. Based on these considerations, three compounds would be suitable for further evaluation. While these results provide a foundation for future work, in vivo pharmacokinetic, pharmacodynamics, and safety studies are needed before BKI compounds can be recommended for clinical use in T. equi infected horses.
- Subjects :
- 0301 basic medicine
Drug
media_common.quotation_subject
hERG
Antiprotozoal Agents
Pharmacology
Biology
Article
03 medical and health sciences
In vivo
Babesiosis
Theileria
Animals
Humans
Potency
Horses
Protein Kinase Inhibitors
media_common
EC50
Imidocarb
Cardiotoxicity
General Veterinary
General Medicine
In vitro
Theileriasis
030104 developmental biology
Pharmacodynamics
biology.protein
Cattle
Horse Diseases
Parasitology
Subjects
Details
- ISSN :
- 03044017
- Volume :
- 251
- Database :
- OpenAIRE
- Journal :
- Veterinary Parasitology
- Accession number :
- edsair.doi.dedup.....64e57d42c31cc6c6f1d0aa3ba5fadcd8