A high throughput screen for next-generation leads targeting malaria parasite transmission.
Resumen: Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies,
highlighting the need for new drugs with alternative modes of action. Since only 0.2–1% of
asexual parasites differentiate into sexual, transmission-competent forms, targeting this
natural bottleneck provides a tangible route to interrupt disease transmission and mitigate
resistance selection. Here we present a high-throughput screen of gametogenesis against a
~70,000 compound diversity library, identifying seventeen drug-like molecules that target
transmission. Hit molecules possess varied activity profiles including male-specific, dual
acting male–female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-
yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo
efficacy. Development of leads with modes of action focussed on the sexual stages of malaria
parasite development provide a previously unexplored base from which future therapeutics
can be developed, capable of preventing parasite transmission through the population.
Identificador universal: https://hdl.handle.net/10641/3613
Fecha: 2018
Ficheros en el ítem
Ficheros | Tamaño | Formato | Ver |
---|---|---|---|
Nature2018.pdf | 3.810Mb | Ver/ |
Este ítem aparece en la(s) siguiente(s) colección(ones)
- MEDICINA [816]