Histone methyltransferases inhibitors against Babesia in vitro

Abstract

Abstract Babesiosis causes negative impact on health of human, domestic animals and wildlife. Currently, the limited strategies of immunoprophylaxis and chemotherapy hinder effective control of babesiosis. In this study, an in vitro screening assay was performed to identify compounds targeting to histone methyltransferase and showing high performance against growth of Babesia sp. Xinjiang (Bxj). We also evaluated their cytotoxicity on MDOK cell line. Eight compounds showed variable degrees of antibabesial activity. Among these, Furamidine showed outstanding activity at nanomolar level of half inhibitive concentration (IC50) in vitro. It also showed low cytotoxicity, of which 50% growth inhibition (CGI50) on MDOK cell line was ~ 100 µM at 24 h, ~ 45 µM at 48 h and ~ 40 µM 72 h. The selective index (SI) (calculated by CGI50/IC50) was higher than 1,500. Our findings support that histone methyltransferases are potential targets for developing alternative drugs to control babesiosis.