Abstract
Some arylmethyloxyphenyl derivatives were prepared as simplified structures of analogous arylpiperazines with high affinity toward dopaminergic D(2) and serotonergic 5-HT(1A) receptors and inhibiting P-glycoprotein (P-gp). The compounds 5b and 8b displayed good P-gp inhibition activity measured as [(3)H]vinblastine transport inhibition in the Caco-2 cell monolayer and intracellular doxorubicin accumulation in MCF7/Adr cells by flow cytometry. Compounds 5b and 8b also inhibited, dose-dependently, ATP-ase activation induced by P-gp substrate vinblastine.
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
-
Adenosine Triphosphatases / metabolism
-
Adenosine Triphosphate / metabolism
-
Antibiotics, Antineoplastic / metabolism
-
Antineoplastic Agents, Phytogenic / metabolism
-
Biological Transport, Active / drug effects
-
Caco-2 Cells
-
Cell Line
-
Dose-Response Relationship, Drug
-
Doxorubicin / metabolism
-
Flow Cytometry
-
Humans
-
Piperazines / chemistry*
-
Piperazines / pharmacology*
-
Receptor, Serotonin, 5-HT1A / metabolism
-
Receptors, Dopamine D2 / drug effects
-
Vinblastine / metabolism
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
Antibiotics, Antineoplastic
-
Antineoplastic Agents, Phytogenic
-
Piperazines
-
Receptors, Dopamine D2
-
Receptor, Serotonin, 5-HT1A
-
Vinblastine
-
Doxorubicin
-
Adenosine Triphosphate
-
Adenosine Triphosphatases