Procainamide-SAHA Fused Inhibitors of hHDAC6 Tackle Multidrug-Resistant Malaria Parasites.
Antimalarials
/ chemical synthesis
Dose-Response Relationship, Drug
Drug Resistance, Multiple
/ drug effects
Histone Deacetylase 6
/ antagonists & inhibitors
Histone Deacetylase Inhibitors
/ chemical synthesis
Hydroxamic Acids
/ chemistry
Malaria, Falciparum
/ drug therapy
Molecular Structure
Plasmodium falciparum
/ drug effects
Procainamide
/ chemistry
Structure-Activity Relationship
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
22 07 2021
22 07 2021
Historique:
pubmed:
30
6
2021
medline:
7
10
2021
entrez:
29
6
2021
Statut:
ppublish
Résumé
Epigenetic post-translational modifications are essential for human malaria parasite survival and progression through its life cycle. Here, we present new functionalized suberoylanilide hydroxamic acid (SAHA) derivatives that chemically combine the pan-histone deacetylase inhibitor SAHA with the DNA methyltransferase inhibitor procainamide. A three- or four-step chemical synthesis was designed starting from cheap raw materials. Compared to the single drugs, the combined molecules showed a superior activity in
Identifiants
pubmed: 34185525
doi: 10.1021/acs.jmedchem.1c00821
doi:
Substances chimiques
Antimalarials
0
Histone Deacetylase Inhibitors
0
Hydroxamic Acids
0
HDAC6 protein, human
EC 3.5.1.98
Histone Deacetylase 6
EC 3.5.1.98
Procainamide
L39WTC366D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM