In Vitro Inhibitory Effects and Bioinformatic Analysis of Norfloxacin and Ofloxacin on Piroplasm

Purpose: 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).Methods: 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.Results: 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.Conclusion: This study helped in discovery novel potent antibabesial combination therapies consist of norfloxacin/ofloxacin, norfloxacin/luteolin, and ofloxacin/PYR.

Automated summary

This study evaluated the inhibitory effect of the fluroquinolone antibiotics norfloxacin and ofloxacin on the growth of various Babesia and Theileria parasites. It also analyzed the structural similarity between these drugs and commonly used antibabesial drugs. The results showed that both norfloxacin and ofloxacin inhibited the growth of Babesia bovis, B. bigemina, B. caballi, and Theileria equi in vitro, with the best effect observed on T. equi. The combination therapies of norfloxacin/luteolin and ofloxacin/PYR showed synergistic interaction against B. bovis and T. equi.