Abstract:
:During screening for the flavonoid chemosensitizers, it was found that 5,7,3',4',5'-pentamethoxyflavone (PMF) was equipotent to verapamil in vitro with respect to the chemosensitizing effect. PMF appears to have a chemosensitizing effect not only by increasing the intracellular accumulation of the drugs without competition in a binding site of azidopine but also by interfering with the substrate-stimulated ATPase activity. Structure-activity relationship suggests that methoxylated substitution and its numbers or sites of the rings are more important than its hydroxylated counterparts in chemosensitization. Overall, PMF is anticipated to be a novel and highly potent second-generation flavonoid chemosensitizer because PMF has significant advantages of having a high therapeutic index, of being a non-transportable inhibitor, and of having a low possibility of drug interactions at the azidopine-binding site of Pgp.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Choi CH,Kim JH,Kim SHdoi
10.1016/j.bbrc.2004.06.020subject
Has Abstractpub_date
2004-07-30 00:00:00pages
672-9issue
3eissn
0006-291Xissn
1090-2104pii
S0006291X04012951journal_volume
320pub_type
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