Tariquidar-related triazoles as potent, selective and stable inhibitors of ABCG2 (BCRP).
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ antagonists & inhibitors
Dose-Response Relationship, Drug
Humans
KB Cells
MCF-7 Cells
Molecular Structure
Neoplasm Proteins
/ antagonists & inhibitors
Quinolines
/ chemical synthesis
Structure-Activity Relationship
Triazoles
/ chemical synthesis
Tumor Cells, Cultured
ABCG2 transporter
ATPase
BCRP
Hoechst33342
Inhibitors
Multidrug resistance
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:
01 Apr 2020
01 Apr 2020
Historique:
received:
31
10
2019
revised:
04
02
2020
accepted:
06
02
2020
pubmed:
28
2
2020
medline:
5
11
2020
entrez:
28
2
2020
Statut:
ppublish
Résumé
Tariquidar derivatives have been described as potent and selective ABCG2 inhibitors. However, their susceptibility to hydrolysis limits their applicability. The current study comprises the synthesis and characterization of novel tariquidar-related inhibitors, obtained by bioisosteric replacement of the labile moieties in our previous tariquidar analog UR-ME22-1 (9). CuAAC ("click" reaction) gave convenient access to a triazole core as a substitute for the labile amide group and the labile ester moiety was replaced by different acyl groups in a Sugasawa reaction. A stability assay proved the enhancement of the stability in blood plasma. Compounds UR-MB108 (57) and UR-MB136 (59) inhibited ABCG2 in a Hoechst 33342 transport assay with an IC
Identifiants
pubmed: 32105979
pii: S0223-5234(20)30100-8
doi: 10.1016/j.ejmech.2020.112133
pii:
doi:
Substances chimiques
ABCG2 protein, human
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Neoplasm Proteins
0
Quinolines
0
Triazoles
0
tariquidar
J58862DTVD
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112133Informations 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.