Back to Search
Start Over
DNA Methylation Bisubstrate Inhibitors Are Fast-Acting Drugs Active against Artemisinin-Resistant Plasmodium falciparum Parasites.
- Source :
-
ACS central science [ACS Cent Sci] 2020 Jan 22; Vol. 6 (1), pp. 16-21. Date of Electronic Publication: 2019 Nov 27. - Publication Year :
- 2020
-
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 activity at 10 mg/kg. These potent inhibitors are a new starting point to develop fast-acting antimalarials that could be used in combination with artemisinins.<br />Competing Interests: The authors declare no competing financial interest.<br /> (Copyright © 2019 American Chemical Society.)
Details
- Language :
- English
- ISSN :
- 2374-7943
- Volume :
- 6
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- ACS central science
- Publication Type :
- Academic Journal
- Accession number :
- 31989022
- Full Text :
- https://doi.org/10.1021/acscentsci.9b00874