DNA Methylation Bisubstrate Inhibitors Are Fast-Acting Drugs Active against Artemisinin-Resistant Plasmodium falciparum Parasites.

ABSTRACT: Malaria is the deadliest parasitic disease affecting over 200 million people worldwide. The increasing number of treatment failures due to multi-drug-resistant parasites in South-East Asia hinders the efforts for elimination. It is thus urgent to develop new antimalarials to contain these resistant parasites. Based on a previous report showing the presence of DNA methylation in Plasmodium, we generated new types of DNA methylation inhibitors against malaria parasites. The quinoline-quinazoline-based inhibitors kill parasites, including artemisinin-resistant field isolates adapted to culture, in the low nanomolar range. The compounds target all stages of the asexual cycle, including early rings, during a 6 h treatment period; they reduce DNA methylation in the parasite and show in vivo acti

SUBMITTER: Nardella F 

PROVIDER: S-EPMC6978834 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature