1,3-Diphenylureido hydroxamate as a promising scaffold for generation of potent antimalarial histone deacetylase inhibitors.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 Nov 2023
29 Nov 2023
Historique:
received:
17
08
2023
accepted:
20
11
2023
medline:
1
12
2023
pubmed:
30
11
2023
entrez:
29
11
2023
Statut:
epublish
Résumé
We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a-d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro, mechanistic studies demonstrated target activity for PfHDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c, 7c, and 8c, identified as the most active in phenotypic assays and PfHDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of PfHDAC1, with an IC
Identifiants
pubmed: 38030668
doi: 10.1038/s41598-023-47959-z
pii: 10.1038/s41598-023-47959-z
pmc: PMC10687260
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Antimalarials
0
Hydroxamic Acids
0
Folic Acid Antagonists
0
Histone Deacetylase 1
EC 3.5.1.98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21006Subventions
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2021/08260-8
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2018/08820-0
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2017/26358-0
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2021/00124-8
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2021/11606-3
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2018/18257-1
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2015/26722-8
Organisme : Deutsche Forschungsgemeinschaft
ID : 471614207
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 301524/2019-0
Organisme : Bundesministerium für Bildung und Forschung
ID : TüCAD2 and CMIF (EXC2124)
Informations de copyright
© 2023. The Author(s).
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