Nucleotide analogues containing a pyrrolidine, piperidine or piperazine ring: Synthesis and evaluation of inhibition of plasmodial and human 6-oxopurine phosphoribosyltransferases and in vitro antimalarial activity.
Antimalarials
/ chemical synthesis
Cell Line
Cell Survival
/ drug effects
Drug Evaluation, Preclinical
Drug Resistance
/ drug effects
Enzyme Inhibitors
/ chemistry
Erythrocytes
/ cytology
Humans
Nucleotides
/ chemistry
Pentosyltransferases
/ antagonists & inhibitors
Piperazine
/ chemistry
Piperidines
/ chemistry
Plasmodium falciparum
/ drug effects
Plasmodium vivax
/ enzymology
Prodrugs
/ chemical synthesis
Protozoan Proteins
/ antagonists & inhibitors
Pyrrolidines
/ chemistry
Structure-Activity Relationship
HG(X)PRT
Hypoxanthine-guanine-(xanthine) phosphoribosyltransferase
Nucleoside phosphonates
Phosphoroamidate prodrug
Plasmodium falciparum
Plasmodium vivax
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 Jul 2021
05 Jul 2021
Historique:
received:
07
12
2020
revised:
24
03
2021
accepted:
25
03
2021
pubmed:
23
4
2021
medline:
12
8
2021
entrez:
22
4
2021
Statut:
ppublish
Résumé
Parasites of the Plasmodium genus are unable to produce purine nucleotides de novo and depend completely on the salvage pathway. This fact makes plasmodial hypoxanthine-guanine-(xanthine) phosphoribosyltransferase [HG(X)PRT] a valuable target for development of antimalarial agents. A series of nucleotide analogues was designed, synthesized and evaluated as potential inhibitors of Plasmodium falciparum HGXPRT, P. vivax HGPRT and human HGPRT. These novel nucleoside phosphonates have a pyrrolidine, piperidine or piperazine ring incorporated into the linker connecting the purine base to a phosphonate group(s) and exhibited a broad range of K
Identifiants
pubmed: 33887682
pii: S0223-5234(21)00265-8
doi: 10.1016/j.ejmech.2021.113416
pii:
doi:
Substances chimiques
Antimalarials
0
Enzyme Inhibitors
0
Nucleotides
0
Piperidines
0
Prodrugs
0
Protozoan Proteins
0
Pyrrolidines
0
Piperazine
1RTM4PAL0V
Pentosyltransferases
EC 2.4.2.-
hypoxanthine-guanine-xanthine phosphoribosyltransferase
EC 2.4.2.-
pyrrolidine
LJU5627FYV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113416Informations de copyright
Copyright © 2021 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.