Benzo[a]phenoxazines: a new group of potent P-glycoprotein inhibitors.
The ability of fifteen novel phenoxazine derivatives (four phenoxazines and eleven benzo[a]phenoxazines) to modulate multidrug resistance (MDR) in a P-gp-overexpressing mouse T lymphoma cell line (L5178 MDR) was studied. A flow cytometric functional test, based on the differential accumulation of rhodamine 123 by sensitive and multidrug-resistant cells, was employed. Seven benzo[a]phenoxazines were observed to increase the amount of rhodamine 123 accumulated by resistant cells, i.e. to be new effective MDR modulators. The results allowed us to draw preliminary conclusions about the structural features of benzo[a]phenoxazines which are important for MDR modulation.
Wesolowska
Olga
O
Department of Biophysics, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland. olawes@biofiz.am.wroc.pl
Molnar
Joseph
J
Westman
Gunnar
G
Samuelsson
Kristin
K
Kawase
Masami
M
Ocsovszki
Imre
I
Motohashi
Noboru
N
Michalak
Krystyna
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D010078:Oxazines / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010078:Oxazines; C039203:phenoxazine