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Inhibitory effects of novel ciprofloxacin derivatives on the growth of four Babesia species and Theileria equi

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Abstract

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-resistant Mycobacterium tuberculosis was 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) on Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi were 32.9, 13.7, 14.9, and 30.9; 14.9, 25.8, 13.6, and 27.5; 34.9, 33.9, 21.1, and 22.3; 26.7, 28.3, 34.5, and 29.1; and 4.7, 26.6, 33.9, and 29.1 μM, 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 μM). 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 IC50 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.

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Acknowledgments

The authors would like to thank Prof. Oriel M.M. Thekisoe.

Funding

This study was supported by the Ministry of Higher Education Egypt, the Japanese Society for the Promotion of Science, and the Ministry of Education, Culture, Sports, Science and Technology, Japan (JSPS) (KAKEN Grant Number 18H02337).

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Authors and Affiliations

  1. National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan

    Gaber El-Saber Batiha, Dickson Stuart Tayebwa, Amany Magdy Beshbishy, Naoaki Yokoyama & Ikuo Igarashi

  2. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Al-Beheira, 22511, Egypt

    Gaber El-Saber Batiha

  3. Research Center for Tick and Tick-borne diseases, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, PO Box 7062, Kampala, Uganda

    Dickson Stuart Tayebwa

  4. Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom, South Africa

    David D. N’Da

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  1. Gaber El-Saber Batiha
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  2. Dickson Stuart Tayebwa
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  3. Amany Magdy Beshbishy
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Correspondence to Ikuo Igarashi.

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All experiments were carried out in conformity with the local guidelines for animal experiments, as approved by the Obihiro University of Agriculture and Veterinary Medicine, Japan (accession number of the animal experiment 28-111-2/28-110). This ethical approval was developed through the basic guidelines for the proper conduct of animal experimentation and related activities in Academic Research Institutions, Ministry of Education, Culture, Sports and Technology (MEXT), Japan.

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Batiha, G.ES., Tayebwa, D.S., Beshbishy, A.M. et al. Inhibitory effects of novel ciprofloxacin derivatives on the growth of four Babesia species and Theileria equi. Parasitol Res 119, 3061–3073 (2020). https://doi.org/10.1007/s00436-020-06796-z

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