Rizk Mohamed Abdo, El-Sayed Shimaa Abd El-Salam, Igarashi Ikuo
Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido, Japan.
Acta Parasitol. 2023 Mar;68(1):213-222. doi: 10.1007/s11686-022-00648-9. Epub 2022 Dec 21.
The in vitro inhibitory effect of two fluroquinolone antibiotics, norfloxacin and ofloxacin, was evaluated in this study on the growth of several Babesia and Theileria parasites with highlighting the bioinformatic analysis for both drugs with the commonly used antibabesial drug, diminazene aceturate (DA), and the recently identified antibabesial drugs, luteolin, and pyronaridine tetraphosphate (PYR).
The antipiroplasm efficacy of screened fluroquinolones in vitro and in vivo was assessed using a fluorescence-based SYBR Green I assay. Using atom Pair signatures, we investigated the structural similarity between fluroquinolones and the antibabesial drugs.
Both fluroquinolones significantly inhibited (P < 0.05) the in vitro growths of Babesia bovis (B. bovis), B. bigemina, B. caballi, and Theileria equi (T. equi) in a dose-dependent manner. The best inhibitory effect for both drugs was observed on the growth of T. equi. Atom Pair fingerprints (APfp) results and AP Tanimoto values revealed that both fluroquinolones, norfloxacin with luteolin, and ofloxacin with PYR, showed the maximum structural similarity (MSS). Two drug interactions findings confirmed the synergetic interaction between these combination therapies against the in vitro growth of B. bovis and T. equi.
This study helped in discovery novel potent antibabesial combination therapies consist of norfloxacin/ofloxacin, norfloxacin/luteolin, and ofloxacin/PYR.
本研究评估了两种氟喹诺酮类抗生素诺氟沙星和氧氟沙星对几种巴贝斯虫和泰勒虫寄生虫生长的体外抑制作用，并着重对这两种药物与常用抗巴贝斯虫药物乙酰马杜霉素（DA）以及最近鉴定出的抗巴贝斯虫药物木犀草素和磷酸咯萘啶（PYR）进行生物信息学分析。
使用基于荧光的SYBR Green I检测法评估筛选出的氟喹诺酮类药物在体外和体内的抗梨形虫功效。利用原子对特征，我们研究了氟喹诺酮类药物与抗巴贝斯虫药物之间的结构相似性。
两种氟喹诺酮类药物均以剂量依赖性方式显著抑制（P < 0.05）牛巴贝斯虫（B. bovis）、双芽巴贝斯虫、马巴贝斯虫和马泰勒虫（T. equi）的体外生长。观察到这两种药物对马泰勒虫的生长具有最佳抑制效果。原子对指纹（APfp）结果和AP塔尼莫托值显示，两种氟喹诺酮类药物，即诺氟沙星与木犀草素以及氧氟沙星与磷酸咯萘啶，表现出最大结构相似性（MSS）。两项药物相互作用研究结果证实了这些联合疗法对牛巴贝斯虫和马泰勒虫体外生长具有协同相互作用。
本研究有助于发现由诺氟沙星/氧氟沙星、诺氟沙星/木犀草素和氧氟沙星/磷酸咯萘啶组成的新型高效抗巴贝斯虫联合疗法。
