The treatment of bovine and equine
piroplasmosis is limited to
diminazene aceturate (DA) and
imidocarb dipropionate. To address this challenge, we need to explore novel
drug compounds and targets. Topoisomerases are potential
drug targets because they play a vital role in solving topological errors of
DNA strands during replication. This study documented the effectiveness of
topoisomerase inhibitors,
nitidine chloride (NC) and
camptothecin (
Cpt), on the growth of Babesia and Theileria parasites. The half maximal inhibitory concentrations (IC50s) against B. bovis, B. bigemina, B. caballi, and T. equi were 1.01 ± 0.2, 5.34 ± 1.0, 0.11 ± 0.03, and 2.05 ± 0.4 μM for NC and 11.67 ± 1.6, 4.00 ± 1.0, 2.07 ± 0.6, and 0.33 ± 0.02 μM for
Cpt, respectively. The viability experiment revealed that 4, 10, and 4 μM treatments of NC or 48, 8, and 8 μM treatments of
Cpt were sufficient to stop the in vitro regrowth of B. bovis, B. bigemina, and B. caballi, respectively. However, T. equi regrew in all of the concentrations used. Moreover, increasing the concentration of NC and
Cpt to 16 μM and 1.2 μM (8 × IC50) did not eliminate T. equi. The micrographs of B. bigemina and B. caballi taken at 24 h and 72 h showed deformed merozoites and remnants of parasites within the red blood cell (RBC), respectively. The treatments of 25 mg/kg DA and 20 mg/kg NC administered intraperitoneally and 20 mg/kg NC given orally showed 93.7, 90.7, and 83.6% inhibition against Babesia microti (B. microti), respectively, compared to the untreated group on day 8. In summary, NC and
Cpt were effective against Babesia and Theileria parasites in vitro. Moreover, 20 mg/kg NC administered intraperitoneally was as effective as 25 mg/kg DA against B. microti in mice and showed no toxic symptoms in mice. The results indicate that NC may, after further evaluations, prove to be an alternative
drug against bovine and equine
piroplasmoses.