Epigenetic inhibitors target multiple stages of Plasmodium falciparum parasites.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 02 2020
11 02 2020
Historique:
received:
08
11
2019
accepted:
16
12
2019
entrez:
13
2
2020
pubmed:
13
2
2020
medline:
11
11
2020
Statut:
epublish
Résumé
The epigenome of the malaria parasite, Plasmodium falciparum, is associated with regulation of various essential processes in the parasite including control of proliferation during asexual development as well as control of sexual differentiation. The unusual nature of the epigenome has prompted investigations into the potential to target epigenetic modulators with novel chemotypes. Here, we explored the diversity within a library of 95 compounds, active against various epigenetic modifiers in cancerous cells, for activity against multiple stages of P. falciparum development. We show that P. falciparum is differentially susceptible to epigenetic perturbation during both asexual and sexual development, with early stage gametocytes particularly sensitive to epi-drugs targeting both histone and non-histone epigenetic modifiers. Moreover, 5 compounds targeting histone acetylation and methylation show potent multistage activity against asexual parasites, early and late stage gametocytes, with transmission-blocking potential. Overall, these results warrant further examination of the potential antimalarial properties of these hit compounds.
Identifiants
pubmed: 32047203
doi: 10.1038/s41598-020-59298-4
pii: 10.1038/s41598-020-59298-4
pmc: PMC7012883
doi:
Substances chimiques
Enzyme Inhibitors
0
Small Molecule Libraries
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2355Références
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