Arylmethyloxyphenyl derivatives: small molecules displaying P-glycoprotein inhibition.
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.
Colabufo
Nicola Antonio
NA
Dipartimento Farmacochimico, Università degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy. colabufo@farmchim.uniba.it
Berardi
Francesco
F
Perrone
Roberto
R
Rapposelli
Simona
S
Digiacomo
Maria
M
Balsamo
Aldo
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D014747:Vinblastine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D010879:Piperazines; D017448:Receptors, Dopamine D2; D044282:Receptor, Serotonin, 5-HT1A; D014747:Vinblastine; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases