Inhibitory effects of novel ciprofloxacin derivatives on the growth of four Babesia species and Theileria equi
Inhibitory effects of novel ciprofloxacin derivatives on the growth of four Babesia species and Theileria equi
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DOI：
10.1007/s00436-020-06796-z
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发表时间：
2020-07-16
影响因子：
2
通讯作者：
Igarashi, Ikuo
中科院分区：
文献类型：
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作者：
Batiha, Gaber El-Saber;Tayebwa, Dickson Stuart;Igarashi, Ikuo
寄生虫抗性的问题以及对大多数市售抗梨浆药物的有毒残留严重削弱了它们的有效性、治疗性和环境安全性。因此，很明显，发展梨形虫病的治疗方案对于改善疾病治疗和控制至关重要。环丙沙星是一种广谱抗生素，主要通过抑制DNA旋转酶和拓扑异构酶来靶向DNA复制机制。因此，环丙沙星用于治疗几种细菌和寄生虫感染。本研究评价了15种抗耐药结核分枝杆菌的新型环丙沙星衍生物（NCD）体外抗梨形虫的效果。NCD最有效的五种化合物的半数最大抑制浓度（IC_（50））值（3、5、10、14、15）对牛巴伯虫、二联巴伯虫、卡氏巴伯虫和马泰勒虫的敏感性分别为32.9、13.7、14.9和30.9; 14.9、25.8、13.6和27.5; 34.9、33.9、21.1和22.3; 26.7、28.3、34.5和29.1 μ M; 4.7、26.6、33.9和29.1 μ M。使用小鼠胚胎成纤维细胞（NIH/3 T3）和Madin-Darby牛肾（MDBK）细胞系评估了受试NCD对宿主细胞的可能有害影响。测试的NCD不抑制NIH/3 T3和MDBK细胞活力，即使在使用的最高浓度（500 μ M）下。确定的最有效的化合物NCD/乙酰氨基二氮烯（DA），阿托伐醌（AQ），和/氯法齐明（CF）的组合治疗主要表现出协同和累加效应。NCD的IC（50）值表明它们是有希望的未来抗梨形虫的候选物。需要进一步的体内试验来评估NCD的治疗潜力。
The problems of parasite resistance, as well as the toxic residues to most of the commercially available antipiroplasmic drugs severely weaken their effective, curative, and environmental safe employment. Therefore, it is clear that the development of treatment options for piroplasmosis is vital for improving disease treatment and control. Ciprofloxacin is a broad-spectrum antibiotic that targets mainly the DNA replication machinery by inhibiting DNA gyrase and topoisomerase enzymes. As a result, ciprofloxacin is used for treating several bacterial and parasitic infections. In this study, the efficacy of 15 novel ciprofloxacin derivatives (NCD) that had been developed against drug-resistantMycobacterium tuberculosiswas evaluated against piroplasm parasite multiplication in vitro. The half-maximal inhibitory concentration (IC50) values of the most effective five compounds of NCD (No. 3,5,10,14,15) onBabesia bovis,Babesia bigemina,Babesia caballi, andTheileria equiwere32.9,13.7,14.9, and30.9;14.9,25.8,13.6, and27.5;34.9,33.9,21.1, and22.3;26.7,28.3,34.5, and29.1; and4.7,26.6,33.9, and29.1 mu M, respectively. Possible detrimental effects of tested NCD on host cells were assessed using mouse embryonic fibroblast (NIH/3T3) and Madin-Darby bovine kidney (MDBK) cell lines. Tested NCD did not suppress NIH/3T3 and MDBK cell viability, even at the highest concentration used (500 mu M). Combination treatments of the identified most effective compounds of NCD/diminazene aceturate (DA), /atovaquone (AQ), and /clofazimine (CF) showed mainly synergistic and additive effects. The IC(50)values of NCD showed that they are promising future candidates against piroplasmosis. Further in vivo trials are required to evaluate the therapeutic potential of NCD.