Benzo[a]phenoxazines: A New Group of Potent P-glycoprotein Inhibitors

• Published in: In vivo (Athens) Vol. 20; no. 1; p. 109
• Main Authors: Wesolowska, Olga, Molnar, Joseph, Westman, Gunnar, Samuelsson, Kristin, Kawase, Masami, Ocsovszki, Imre, Motohashi, Noboru, Michalak, Krystyna
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01-01-2006
• Subjects: ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Oxazines - pharmacology
• ISSN: 0258-851X; 1791-7549

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.