Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi
Abstract Background The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-020-04487-3 |
| _version_ | 1819075940932648960 |
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| author | Marta G. Silva Reginaldo G. Bastos J. Stone Doggett Michael K. Riscoe Sovitj Pou Rolf Winter Rozalia A. Dodean Aaron Nilsen Carlos E. Suarez |
| author_facet | Marta G. Silva Reginaldo G. Bastos J. Stone Doggett Michael K. Riscoe Sovitj Pou Rolf Winter Rozalia A. Dodean Aaron Nilsen Carlos E. Suarez |
| author_sort | Marta G. Silva |
| collection | DOAJ |
| description | Abstract Background The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. The endochin-like quinolones (ELQ)-300 and ELQ-316 have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp., with ELQ-316 also being effective against Babesia microti, without showing toxicity in mammals. Methods The inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. The percentage of parasitized erythrocytes was measured by flow cytometry, and the effect of the ELQ compounds on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay. Results We calculated the half maximal inhibitory concentration (IC50) at 72 h, which ranged from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 among all cultured parasites tested at 72 h. None of the parasites tested were able to replicate in cultures in the presence of ELQ-300 and ELQ-316 at the maximal inhibitory concentration (IC100), which ranged from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing. Conclusions The compounds ELQ-300 and ELQ-316 showed significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis. |
| first_indexed | 2024-12-21T18:33:24Z |
| format | Article |
| id | doaj.art-35a9dec597be472688855738dda6a7d7 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-12-21T18:33:24Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-35a9dec597be472688855738dda6a7d72022-12-21T18:54:13ZengBMCParasites & Vectors1756-33052020-12-0113111110.1186/s13071-020-04487-3Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equiMarta G. Silva0Reginaldo G. Bastos1J. Stone Doggett2Michael K. Riscoe3Sovitj Pou4Rolf Winter5Rozalia A. Dodean6Aaron Nilsen7Carlos E. Suarez8Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State UniversityDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State UniversityOregon Health and Science UniversityOregon Health and Science UniversityVA Portland Health Care SystemVA Portland Health Care SystemVA Portland Health Care SystemOregon Health and Science UniversityDepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State UniversityAbstract Background The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. The endochin-like quinolones (ELQ)-300 and ELQ-316 have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp., with ELQ-316 also being effective against Babesia microti, without showing toxicity in mammals. Methods The inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. The percentage of parasitized erythrocytes was measured by flow cytometry, and the effect of the ELQ compounds on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay. Results We calculated the half maximal inhibitory concentration (IC50) at 72 h, which ranged from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 among all cultured parasites tested at 72 h. None of the parasites tested were able to replicate in cultures in the presence of ELQ-300 and ELQ-316 at the maximal inhibitory concentration (IC100), which ranged from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing. Conclusions The compounds ELQ-300 and ELQ-316 showed significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.https://doi.org/10.1186/s13071-020-04487-3Bovine babesiosisEquine piroplamsosisBabesia bovisBabesia bigeminaBabesia caballiTheileria equi |
| spellingShingle | Marta G. Silva Reginaldo G. Bastos J. Stone Doggett Michael K. Riscoe Sovitj Pou Rolf Winter Rozalia A. Dodean Aaron Nilsen Carlos E. Suarez Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi Parasites & Vectors Bovine babesiosis Equine piroplamsosis Babesia bovis Babesia bigemina Babesia caballi Theileria equi |
| title | Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi |
| title_full | Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi |
| title_fullStr | Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi |
| title_full_unstemmed | Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi |
| title_short | Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi |
| title_sort | endochin like quinolone 300 and elq 316 inhibit babesia bovis b bigemina b caballi and theileria equi |
| topic | Bovine babesiosis Equine piroplamsosis Babesia bovis Babesia bigemina Babesia caballi Theileria equi |
| url | https://doi.org/10.1186/s13071-020-04487-3 |
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