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© Yang SI, Institut Pasteur
Publication : ACS central science

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in ACS central science - 27 Nov 2019

Nardella F, Halby L, Hammam E, Erdmann D, Cadet-Daniel V, Peronet R, Ménard D, Witkowski B, Mecheri S, Scherf A, Arimondo PB

Link to Pubmed [PMID] – 31989022

ACS Cent Sci 2020 Jan;6(1):16-21

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 , 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 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.

https://www.ncbi.nlm.nih.gov/pubmed/31989022