Furamidine, a methyltransferase inhibitor, is a potential anti-Babesia spp. chemotherapeutic.

Epigenetic inhibitors targeting histone methyltransferases (HMTs) have been proven to be promising for blood protozoan treatment. However, little is known about the effects of HMT inhibitors on Babesia parasites. Here, in vitro and in vivo drug tests were performed to evaluate the efficacy of several compounds targeting various HMTs for Babesia treatment. Their cytotoxicity to MDOK cells was also assessed. Among these compounds, furamidine demonstrated outstanding activity in vitro at the nanomolar level (IC50s of 0.03 ± 0.55, 0.02 ± 0.50, and0.02 ± 0.76 μM at 48, 72, and 96 h, respectively). Furthermore, the IC50 of furamidine on MDOK cells was ~ 100 μM after 24 h, ~ 45 μM after 48 h and ~ 40 μM after 72 h. The therapeutic index of furamidine was greater than 1,500. In addition, furamidine effectively inhibited the growth of B. duncani and B. microti in hamsters and BALB/c mice. Furthermore, furamidine was demonstrated high in vivo safety. These findings suggest that furamidine could be an effective alternative drug for treating babesiosis.