Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi.
Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi.
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DOI：
10.1186/s13071-020-04487-3
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发表时间：
2020-12-03
影响因子：
3.2
通讯作者：
Suarez CE
中科院分区：
文献类型：
--
作者：
Silva MG;Bastos RG;Stone Doggett J;Riscoe MK;Pou S;Winter R;Dodean RA;Nilsen A;Suarez CE
引起牛巴贝斯虫病的最常见的尖端复合体寄生虫是牛巴贝斯虫和二重巴贝斯虫，而卡巴氏巴贝斯虫和马泰勒虫是引起马的梨形虫病的罪魁祸首。这些疾病的治疗和控制通常是使用潜在的毒性化疗药物，如咪达威，但抗药性寄生虫正在出现，需要替代的有效和更安全的药物。内毒素样喹诺酮(ELQ)-300和ELQ-316已被证明对相关顶端复合体(如疟原虫)安全有效，ELQ-316对微小巴贝斯虫也有效，对哺乳动物没有毒性。研究了ELQ-300和ELQ-316对培养的牛黄杆菌、双链杆菌、卡氏杆菌和马牛的生长抑制作用。用流式细胞仪检测红细胞的寄生率，用比色法检测细胞代谢活性，评价ELQ化合物对马和牛外周血单个核细胞(PBMC)活力的影响。我们计算了72小时所有培养的寄生虫对ELQ-300和ELQ-316的半数抑制浓度(IC_(50))，分别为0.04~0.37 nM和0.002~0.1 nM。ELQ-300和ELQ-316分别为1.3~5.7 nM和1.0~6.0 nM，对马、牛PBMC的IC100活性无明显影响。化合物ELQ-300和ELQ-316在宿主细胞可耐受的剂量下，对引起牛巴贝斯虫病和马疫原体病的主要寄生虫表现出显著的抑制活性。这些ELQ药物可能是开发治疗牛巴贝斯虫病和马疫原体病的替代方案的可行候选药物。
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. 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. 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. 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.
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影响因子：
17.1
作者：
Nilsen A;LaCrue AN;White KL;Forquer IP;Cross RM;Marfurt J;Mather MW;Delves MJ;Shackleford DM;Saenz FE;Morrisey JM;Steuten J;Mutka T;Li Y;Wirjanata G;Ryan E;Duffy S;Kelly JX;Sebayang BF;Zeeman AM;Noviyanti R;Sinden RE;Kocken CHM;Price RN;Avery VM;Angulo-Barturen I;Jiménez-Díaz MB;Ferrer S;Herreros E;Sanz LM;Gamo FJ;Bathurst I;Burrows JN;Siegl P;Guy RK;Winter RW;Vaidya AB;Charman SA;Kyle DE;Manetsch R;Riscoe MK
通讯作者：
Riscoe MK
DOI：
10.1016/j.ijpddr.2013.01.003
发表时间：
2013-12-01
影响因子：
4
作者：
Silva, Marta G.;Domingos, Ana;Suarez, Carlos E.
通讯作者：
Suarez, Carlos E.
影响因子：
56.9
作者：
LEVY, MG;RISTIC, M
通讯作者：
RISTIC, M
影响因子：
2.6
作者：
Suarez, Carlos E.;Noh, Susan
通讯作者：
Noh, Susan
影响因子：
3.2
作者：
Wise, L. N.;Kappmeyer, L. S.;Knowles, D. P.
通讯作者：
Knowles, D. P.