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

Flore Nardella | Zendy; Ludovic Halby | Zendy; Elie Hammam | Zendy; Diane Erdmann | Zendy; Véronique Cadet-Daniel | Zendy; Roger Péronet | Zendy; Didier Ménard | Zendy; Benoît Witkowski | Zendy; Salaheddine Mécheri | Zendy; Artur Scherf | Zendy; Paola B. Arimondo | Zendy

Open Access

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

Author(s) -

Flore Nardella,

Ludovic Halby,

Elie Hammam,

Diane Erdmann,

Véronique Cadet-Daniel,

Roger Péronet,

Didier Ménard,

Benoît Witkowski,

Salaheddine Mécheri,

Artur Scherf,

Paola B. Arimondo

Publication year - 2019

Publication title -

acs central science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 4.893

H-Index - 76

eISSN - 2374-7951

pISSN - 2374-7943

DOI - 10.1021/acscentsci.9b00874

Subject(s) - artemisinin , plasmodium falciparum , malaria , biology , chloroquine , methylation , plasmodium (life cycle) , in vivo , dna methylation , pharmacology , dna , parasite hosting , genetics , immunology , gene , gene expression , world wide web , computer science

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research