Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi

Parasites & Vectors

Marta G. Silva¹  Reginaldo G. Bastos¹  Carlos E. Suarez²  J. Stone Doggett³  Michael K. Riscoe³  Aaron Nilsen⁴  Sovitj Pou⁵  Rolf Winter⁵  Rozalia A. Dodean⁵ 

[1] Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA;Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA;Animal Disease Research Unit, Agricultural Research Service, USDA, WSU, Pullman, WA, USA;Oregon Health and Science University, 3181 SW Sam Jackson Blvd., 97239, Portland, Oregon, USA;Oregon Health and Science University, 3181 SW Sam Jackson Blvd., 97239, Portland, Oregon, USA;VA Portland Health Care System, 3710 SW US Veterans Hospital Road, 97239, Portland, OR, USA;VA Portland Health Care System, 3710 SW US Veterans Hospital Road, 97239, Portland, OR, USA;

关键词: Bovine babesiosis;    Equine piroplamsosis;    Babesia bovis;    Babesia bigemina;    Babesia caballi;    Theileria equi;    Endochin-like quinolones;    ELQ-300;    nnELQ-316;   

DOI  :  10.1186/s13071-020-04487-3

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsThe 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.ResultsWe 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.ConclusionsThe 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.

【 授权许可】

CC BY