Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors.
Benzimidazoles
/ pharmacology
Binding Sites
Caco-2 Cells
Cell Line, Tumor
Diabetes Mellitus, Type 2
/ drug therapy
Dipeptidyl Peptidase 4
/ metabolism
Dipeptidyl-Peptidase IV Inhibitors
/ pharmacology
Humans
Hypoglycemic Agents
/ pharmacology
Molecular Docking Simulation
/ methods
Reactive Oxygen Species
/ metabolism
Structure-Activity Relationship
Xanthine Oxidase
/ antagonists & inhibitors
Benzimidazole
Cytotoxicity
Dipeptidyl peptidase-4
Dual inhibition
Molecular dynamics
Xanthine oxidase
Journal
Chemico-biological interactions
ISSN: 1872-7786
Titre abrégé: Chem Biol Interact
Pays: Ireland
ID NLM: 0227276
Informations de publication
Date de publication:
05 Jan 2020
05 Jan 2020
Historique:
received:
03
08
2019
revised:
08
10
2019
accepted:
21
10
2019
pubmed:
2
11
2019
medline:
23
2
2020
entrez:
1
11
2019
Statut:
ppublish
Résumé
Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1-9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo[3,2-a]benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC
Identifiants
pubmed: 31669219
pii: S0009-2797(19)31329-8
doi: 10.1016/j.cbi.2019.108873
pii:
doi:
Substances chimiques
Benzimidazoles
0
Dipeptidyl-Peptidase IV Inhibitors
0
Hypoglycemic Agents
0
Reactive Oxygen Species
0
benzimidazolone
20662-53-7
Xanthine Oxidase
EC 1.17.3.2
DPP4 protein, human
EC 3.4.14.5
Dipeptidyl Peptidase 4
EC 3.4.14.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108873Informations de copyright
Copyright © 2019 Elsevier B.V. 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.