The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro
Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and resi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
| Published: |
MDPI
2024
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.12123/20244 https://www.mdpi.com/1999-4923/16/11/1402 https://doi.org/10.3390/pharmaceutics16111402 |
| _version_ | 1855038193899929600 |
|---|---|
| author | Cardillo, Natalia Marina Villarino, Nicolas F. Lacy, Paul A. Riscoe, Michael K. Doggett, Joseph Stone Ueti, Massaro W. Chung, Chungwon J. Suarez, Carlos |
| author_browse | Cardillo, Natalia Marina Chung, Chungwon J. Doggett, Joseph Stone Lacy, Paul A. Riscoe, Michael K. Suarez, Carlos Ueti, Massaro W. Villarino, Nicolas F. |
| author_facet | Cardillo, Natalia Marina Villarino, Nicolas F. Lacy, Paul A. Riscoe, Michael K. Doggett, Joseph Stone Ueti, Massaro W. Chung, Chungwon J. Suarez, Carlos |
| author_sort | Cardillo, Natalia Marina |
| collection | INTA Digital |
| description | Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ, and their combination treatment could be effective against Babesia bovis in an in vitro culture model and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites starting at 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ + ELQ-316 and ID + ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. The IC50% and IC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Mann–Whitney and Kruskall–Wallis test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p < 0.05) of B. bovis in in vitro cultures. The combination of BPQ + ELQ-316 had the lowest calculated inhibitory concentration 50% (IC50%) values, 31.21 nM (IC95%: 15.06–68.48); followed by BPQ, 77.06 nM (IC95%: 70.16–86.01); ID + ELQ316, 197 nM (IC95%:129.0–311.2); ID, 635.1 nM (IC95%: 280.9–2119); and ELQ316, 654.9 nM (IC95%: 362.3–1411). Conclusions: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis. |
| format | info:ar-repo/semantics/artículo |
| id | INTA20244 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | MDPI |
| publisherStr | MDPI |
| record_format | dspace |
| spelling | INTA202442024-11-12T15:02:33Z The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro Cardillo, Natalia Marina Villarino, Nicolas F. Lacy, Paul A. Riscoe, Michael K. Doggett, Joseph Stone Ueti, Massaro W. Chung, Chungwon J. Suarez, Carlos Babesia bovis Sporozoa Animal Diseases Diseases Control Drugs Livestock Enfermedades de los Animales Control de Enfermedades Medicamentos Ganado Apicomplexa Imidocarb Buparvaquone Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ, and their combination treatment could be effective against Babesia bovis in an in vitro culture model and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites starting at 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ + ELQ-316 and ID + ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. The IC50% and IC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Mann–Whitney and Kruskall–Wallis test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p < 0.05) of B. bovis in in vitro cultures. The combination of BPQ + ELQ-316 had the lowest calculated inhibitory concentration 50% (IC50%) values, 31.21 nM (IC95%: 15.06–68.48); followed by BPQ, 77.06 nM (IC95%: 70.16–86.01); ID + ELQ316, 197 nM (IC95%:129.0–311.2); ID, 635.1 nM (IC95%: 280.9–2119); and ELQ316, 654.9 nM (IC95%: 362.3–1411). Conclusions: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis. EEA Paraná Fil: Cardillo, Natalia Marina. United States Department of Agriculture-Agricultural Research Service. Animal Disease Research Unit; Estados Unidos Fil: Cardillo, Natalia Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Paraná; Argentina. Fil: Cardillo, Natalia Marina. Washington State University. Department of Veterinary Microbiology and Pathology; Estados Unidos Fil: Villarino, Nicolas F. Washington State University. College of Veterinary Medicine. Department of Veterinary Clinical Sciences. Program in Individualized Medicine; Estados Unidos Fil: Lacy, Paul A. United States Department of Agriculture-Agricultural Research Service. Animal Disease Research Unit; Estados Unidos Fil: Riscoe, Michael K. VA Portland Healthcare System; Estados Unidos Fil: Riscoe, Michael K. Oregon Health & Science University. Department of Microbiology and Molecular Immunology; Estados Unidos Fil: Doggett, Joseph Stone. VA Portland Healthcare System; Estados Unidos Fil: Doggett, Joseph Stone. Oregon Health & Science University. School of Medicine. Division of Infectious Diseases; Estados Unidos Fil: Ueti, Massaro W. United States Department of Agriculture-Agricultural Research Service. Animal Disease Research Unit; Estados Unidos Fil: Ueti, Massaro W. Washington State University. Department of Veterinary Microbiology and Pathology; Estados Unidos Fil: Chung, Chungwon J. United States Department of Agriculture-Agricultural Research Service. Animal Disease Research Unit; Estados Unidos Fil: Suarez, Carlos. United States Department of Agriculture-Agricultural Research Service. Animal Disease Research Unit; Estados Unidos Fil: Suarez, Carlos. Washington State University. Department of Veterinary Microbiology and Pathology; Estados Unidos 2024-11-12T15:00:20Z 2024-11-12T15:00:20Z 2024-10 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/20244 https://www.mdpi.com/1999-4923/16/11/1402 1999-4923 https://doi.org/10.3390/pharmaceutics16111402 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf MDPI Pharmaceutics 16 (11) : 1402. (October 2024) |
| spellingShingle | Babesia bovis Sporozoa Animal Diseases Diseases Control Drugs Livestock Enfermedades de los Animales Control de Enfermedades Medicamentos Ganado Apicomplexa Imidocarb Buparvaquone Cardillo, Natalia Marina Villarino, Nicolas F. Lacy, Paul A. Riscoe, Michael K. Doggett, Joseph Stone Ueti, Massaro W. Chung, Chungwon J. Suarez, Carlos The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro |
| title | The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro |
| title_full | The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro |
| title_fullStr | The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro |
| title_full_unstemmed | The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro |
| title_short | The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro |
| title_sort | combination of buparvaquone and elq316 exhibit a stronger effect than elq316 and imidocarb against babesia bovis in vitro |
| topic | Babesia bovis Sporozoa Animal Diseases Diseases Control Drugs Livestock Enfermedades de los Animales Control de Enfermedades Medicamentos Ganado Apicomplexa Imidocarb Buparvaquone |
| url | http://hdl.handle.net/20.500.12123/20244 https://www.mdpi.com/1999-4923/16/11/1402 https://doi.org/10.3390/pharmaceutics16111402 |
| work_keys_str_mv | AT cardillonataliamarina thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT villarinonicolasf thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT lacypaula thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT riscoemichaelk thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT doggettjosephstone thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT uetimassarow thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT chungchungwonj thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT suarezcarlos thecombinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT cardillonataliamarina combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT villarinonicolasf combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT lacypaula combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT riscoemichaelk combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT doggettjosephstone combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT uetimassarow combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT chungchungwonj combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro AT suarezcarlos combinationofbuparvaquoneandelq316exhibitastrongereffectthanelq316andimidocarbagainstbabesiabovisinvitro |