Design, synthesis, and evaluation of substrate - analogue inhibitors of Trypanosoma cruzi ribose 5-phosphate isomerase type B.
3T3 Cells
Aldose-Ketose Isomerases
/ antagonists & inhibitors
Animals
Binding Sites
Catalytic Domain
Drug Design
Enzyme Inhibitors
/ chemistry
Kinetics
Mice
Molecular Dynamics Simulation
Protozoan Proteins
/ antagonists & inhibitors
Substrate Specificity
Trypanocidal Agents
/ chemical synthesis
Trypanosoma cruzi
/ drug effects
Amastigote
Chagas’ disease
Competitive inhibition
Isomerase
Neglected tropical diseases
Substrate-analogue inhibitors
Trypanosoma cruzi
Trypomastigote
Trypsin digestion LC-MS/MS
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
22
09
2020
revised:
17
11
2020
accepted:
23
11
2020
pubmed:
30
11
2020
medline:
11
8
2021
entrez:
29
11
2020
Statut:
ppublish
Résumé
Ribose 5-phosphate isomerase type B (RPI-B) is a key enzyme of the pentose phosphate pathway that catalyzes the isomerization of ribose 5-phosphate (R5P) and ribulose 5-phosphate (Ru5P). Trypanosoma cruzi RPI-B (TcRPI-B) appears to be a suitable drug-target mainly due to: (i) its essentiality (as previously shown in other trypanosomatids), (ii) it does not present a homologue in mammalian genomes sequenced thus far, and (iii) it participates in the production of NADPH and nucleotide/nucleic acid synthesis that are critical for parasite cell survival. In this survey, we report on the competitive inhibition of TcRPI-B by a substrate - analogue inhibitor, Compound B (K
Identifiants
pubmed: 33249135
pii: S0960-894X(20)30834-9
doi: 10.1016/j.bmcl.2020.127723
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Protozoan Proteins
0
Trypanocidal Agents
0
Aldose-Ketose Isomerases
EC 5.3.1.-
ribosephosphate isomerase
EC 5.3.1.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
127723Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.