Rizk Mohamed Abdo, El-Sayed Shimaa Abd El-Salam, El-Alfy El-Sayed, Igarashi Ikuo
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido, 080-8555, Japan.
Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
Acta Parasitol. 2023 Mar;68(1):249-256. doi: 10.1007/s11686-022-00655-w. Epub 2023 Jan 13.
The imidazo[1,2-a] pyridines have huge applications in medicinal chemistry with potent activity against wide spectrum of infectious agents. The efficacy of imidazo[1,2-a]pyridine on the in vitro growth of different piroplasms, including Babesia bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi, was investigated in this study.
The anti-piroplasm efficacy of imidazo[1,2-a] pyridines was assessed using a fluorescence-based SYBR Green I assay. Furthermore, efficacy of imidazo[1,2-a]pyridine against piroplasms following discontinuation of treatment was also assessed using a viability assay. In vitro cultures of B. bovis and T. equi were used to assess the imidazo[1,2-a]pyridine and diminazene aceturate (DA) interaction.
In vitro, imidazo[1,2-a]pyridine inhibited the growth of B. bovis, B. bigemina, B. caballi, and T. equi in a dose-dependent manner. The highest inhibitory effects of imidazo[1,2-a]pyridine were detected on the growth of B. caballi with IC value of 0.47 ± 0.07. Interestingly, the efficacy of imidazo[1,2-a]pyridine was higher against B. bigemina (IC: 1.37 ± 0.15) compared to the positive-control DA (IC: 2.29 ± 0.06). The viability test findings indicate that imidazo[1,2-a]pyridine had a long-lasting inhibitory effect on bovine Babesia parasites in vitro growth up to 4 days after treatment. Notably, when coupled with DA at 0.75 or 0.50 IC, a high concentration (0.75 IC) of imidazo[1,2-a]pyridine produced additive suppression of B. bovis growth which suggest that imidazo[1,2-a]pyridine/DA could be a promising combination therapy for the treatment of B. bovis.
The obtained encouraging findings pave the way for in vitro and in vivo efficacy trials of imidazo[1,2-a]pyridine derivatives against several piroplasmids.
咪唑并[1,2 - a]吡啶在药物化学领域有广泛应用，对多种感染因子具有强大活性。本研究考察了咪唑并[1,2 - a]吡啶对不同梨形虫体外生长的效果，这些梨形虫包括牛巴贝斯虫、双芽巴贝斯虫、分歧巴贝斯虫、马巴贝斯虫和驽巴贝斯虫。
采用基于荧光的SYBR Green I检测法评估咪唑并[1,2 - a]吡啶的抗梨形虫效果。此外，还通过活力检测评估了停药后咪唑并[1,2 - a]吡啶对梨形虫的疗效。利用牛巴贝斯虫和驽巴贝斯虫的体外培养物评估咪唑并[1,2 - a]吡啶与乙酰马啉（DA）的相互作用。
在体外，咪唑并[1,2 - a]吡啶以剂量依赖方式抑制牛巴贝斯虫、双芽巴贝斯虫、马巴贝斯虫和驽巴贝斯虫的生长。咪唑并[1,2 - a]吡啶对马巴贝斯虫生长的抑制作用最强，IC值为0.47±0.07。有趣的是，与阳性对照DA（IC：2.29±0.06）相比，咪唑并[1,2 - a]吡啶对双芽巴贝斯虫的疗效更高（IC：1.37±0.15）。活力测试结果表明，咪唑并[1,2 - a]吡啶在治疗后长达4天对牛巴贝斯虫寄生虫的体外生长具有持久的抑制作用。值得注意的是，当与0.75或0.50 IC的DA联合使用时，高浓度（0.75 IC）的咪唑并[1,2 - a]吡啶对牛巴贝斯虫生长产生相加抑制作用，这表明咪唑并[1,2 - a]吡啶/DA可能是治疗牛巴贝斯虫的一种有前景的联合疗法。
所获得的令人鼓舞的结果为咪唑并[1,2 - a]吡啶衍生物针对多种梨形虫的体外和体内疗效试验铺平了道路。
