Open AccessActivity Comparison of Epigenetic Modulators against the Hemoprotozoan Parasites Babesia divergens and Plasmodium falciparum
Author(s) -
Leen N. Vanheer,
Björn F.C. Kafsack
Publication year - 2021
Publication title -
acs infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.324
H-Index - 39
ISSN - 2373-8227
DOI - 10.1021/acsinfecdis.0c00853
Subject(s) - biology , babesia , plasmodium falciparum , babesiosis , epigenetics , babesia bigemina , malaria , parasitic disease , antiparasitic , plasmodium (life cycle) , protozoa , virology , antiparasitic agent , babesia bovis , disease , immunology , parasite hosting , microbiology and biotechnology , pharmacology , genetics , medicine , gene , pathology , world wide web , computer science
Babesiosis is a tick-borne parasitic disease of humans and livestock that has dramatically increased in frequency and geographical range over the past few decades. Infection of cattle often causes large economic losses, and human infection can be fatal in immunocompromised patients. Unlike for malaria, another disease caused by hemoprotozoan parasites, limited treatment options exist for Babesia infections. As epigenetic regulation is a promising target for new antiparasitic drugs, we screened 324 epigenetic inhibitors against Babesia divergens blood stages and identified 75 (23%) and 17 (5%) compounds that displayed ≥90% inhibition at 10 and 1 μM, respectively, including over a dozen compounds with activity in the low nanomolar range. We observed differential activity of some inhibitor classes against Babesia divergens and Plasmodium falciparum parasites and identified pairs of compounds with a high difference in activity despite a high similarity in chemical structure, highlighting new insights into the development of epigenetic inhibitors as antiparasitic drugs.