Design, Biological Evaluation, and Molecular Modeling of Tetrahydroisoquinoline Derivatives: Discovery of A Potent P-Glycoprotein Ligand Overcoming Multidrug Resistance in Cancer Stem Cells.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ chemistry
Animals
Antineoplastic Agents
/ chemistry
Binding Sites
Cell Line, Tumor
Cell Survival
/ drug effects
Dogs
Doxorubicin
/ pharmacology
Drug Design
Drug Resistance, Neoplasm
/ drug effects
Gene Editing
Humans
Ligands
Madin Darby Canine Kidney Cells
Molecular Dynamics Simulation
Neoplastic Stem Cells
/ cytology
Permeability
/ drug effects
Structure-Activity Relationship
Tetrahydroisoquinolines
/ chemistry
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
24 01 2019
24 01 2019
Historique:
pubmed:
26
12
2018
medline:
18
10
2019
entrez:
26
12
2018
Statut:
ppublish
Résumé
P-Glycoprotein is a well-known membrane transporter responsible for the efflux of an ample spectrum of anticancer drugs. Its relevance in the management of cancer chemotherapy is increased in view of its high expression in cancer stem cells, a population of cancer cells with strong tumor-promoting ability. In the present study, a series of compounds were synthesized through structure modulation of [4'-(6,7-dimethoxy-3,4-dihydro-1 H-isoquinolin-2-ylmethyl)biphenyl-4-ol] (MC70), modifying the phenolic group of the lead compound. Among them, compound 5b emerged for its activity against the transporter (EC
Identifiants
pubmed: 30584838
doi: 10.1021/acs.jmedchem.8b01655
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
Antineoplastic Agents
0
Ligands
0
Tetrahydroisoquinolines
0
Doxorubicin
80168379AG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM