Novel Quinoline Compound Derivatives of NSC23925 as Potent Reversal Agents Against P-Glycoprotein-Mediated Multidrug Resistance.
P-glycoprotein (P-gp)
molecular docking
multidrug resistance (MDR)
quinoline
reversal cancer resistance
Journal
Frontiers in chemistry
ISSN: 2296-2646
Titre abrégé: Front Chem
Pays: Switzerland
ID NLM: 101627988
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
07
2019
accepted:
12
11
2019
entrez:
11
1
2020
pubmed:
11
1
2020
medline:
11
1
2020
Statut:
epublish
Résumé
Multidrug resistance is a serious problem and a common cause of cancer treatment failure, leading to patient death. Although numerous reversal resistance inhibitors have been evaluated in preclinical or clinical trials, efficient and low-toxicity reversal agents have not been identified. In this study, a series of novel quinoline compound derivatives from NSC23925 were designed to inhibit P-glycoprotein (P-gp). Among them, YS-7a showed a stronger inhibitory effect against P-gp than verapamil, as a positive control, when co-incubated with chemotherapy drugs at minimally cytotoxic concentrations. YS-7a suppressed the P-gp transport function without affecting the expression of P-gp but stimulated the ATPase activity of P-gp in a dose-dependent manner. Next, molecular docking was used to predict the six most probable binding sites, namely, SER270, VAL273, VAL274, ILE354, VAL357, and PHE390. Moreover, YS-7a had no effect on cytochrome P450 3A4 activity and showed little toxicity to normal cells. In addition, combined treatment of YS-7a with vincristine showed a better inhibitory effect than the positive control verapamil
Identifiants
pubmed: 31921759
doi: 10.3389/fchem.2019.00820
pmc: PMC6931887
doi:
Types de publication
Journal Article
Langues
eng
Pagination
820Informations de copyright
Copyright © 2019 Quan, Du, Xu, Hou, Gong, Wu, Zhou, Jiang, Lu, Yuan, Yang, Shi and Sun.
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