Design, synthesis, and biological evaluation of aryl piperazines with potential as antidiabetic agents via the stimulation of glucose uptake and inhibition of NADH:ubiquinone oxidoreductase.
Animals
Biological Transport
Cells, Cultured
Dose-Response Relationship, Drug
Drug Design
Enzyme Inhibitors
/ chemical synthesis
Glucose
/ metabolism
Humans
Hypoglycemic Agents
/ chemical synthesis
Mice
Models, Molecular
Molecular Structure
NADH, NADPH Oxidoreductases
/ antagonists & inhibitors
Piperazines
/ chemical synthesis
Structure-Activity Relationship
Complex 1
Diabetes
Glucose uptake
Pharmacokinetics
Piperazine
Structure activity relationship
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:
15 Sep 2020
15 Sep 2020
Historique:
received:
23
08
2019
revised:
29
04
2020
accepted:
29
04
2020
pubmed:
10
7
2020
medline:
2
4
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose uptake compared to vehicle control and micromolar inhibition of NADH:ubiquinone oxidoreductase (IC
Identifiants
pubmed: 32645646
pii: S0223-5234(20)30387-1
doi: 10.1016/j.ejmech.2020.112416
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Hypoglycemic Agents
0
Piperazines
0
NADH, NADPH Oxidoreductases
EC 1.6.-
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112416Informations de copyright
Copyright © 2020 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.