Early identification of promiscuous attributes of aldose reductase inhibitors using a DMSO-perturbation assay.
Aldose reductase inhibitor
Chemically engineered extract
Dimethyl sulfoxide
Nonspecific binding inhibition
Perturbation
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 2020
15 01 2020
Historique:
received:
05
08
2019
revised:
11
10
2019
accepted:
08
11
2019
pubmed:
21
11
2019
medline:
17
2
2021
entrez:
21
11
2019
Statut:
ppublish
Résumé
Aldose reductase (AR) inhibitors are used clinically to treat long-term diabetic complications. Previous studies reported a series of AR inhibitory candidates, but unfortunately the mode of inhibition was poorly described due mainly to the lack of readily available methods for evaluating the specificity. The present study examined the AR inhibitory effects of novel synthetic hydantoins and their structural relatives, some of which were obtained from chemically engineered extracts of natural plants, and discovered several novel AR inhibitors with moderate inhibitory activity. The identified inhibitors were then subjected to a two-step mechanistic characterization using a detergent-addition assay and our novel dimethyl sulfoxide (DMSO)-perturbation assay. The detergent-addition assay revealed aggregation-based inhibitors, and the subsequent DMSO-perturbation assay identified nonspecific binding inhibitors. Thus, the present study demonstrates the usefulness of the DMSO-perturbation screen for identifying nonspecific binding characteristics of AR inhibitors.
Identifiants
pubmed: 31744675
pii: S0960-894X(19)30784-X
doi: 10.1016/j.bmcl.2019.126815
pii:
doi:
Substances chimiques
Aldehyde Reductase
EC 1.1.1.21
Dimethyl Sulfoxide
YOW8V9698H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
126815Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.