dc.contributor.author | Delves, Michael J. | |
dc.contributor.author | León Díaz, María Luisa | |
dc.contributor.author | Baum, Jake | |
dc.date.accessioned | 2023-12-22T11:36:43Z | |
dc.date.available | 2023-12-22T11:36:43Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 0022-2623 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3613 | |
dc.description.abstract | 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. | spa |
dc.language.iso | eng | spa |
dc.publisher | Nature Communications | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | A high throughput screen for next-generation leads targeting malaria parasite transmission. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 3903 KB | spa |
dc.identifier.doi | 10.1038/s41467-018-05777-2 | spa |
dc.relation.publisherversion | https://www.nature.com/articles/s41467-018-05777-2 | spa |