Reversal of P-glycoprotein-mediated MDR by 5,7,3',4',5'-pentamethoxyflavone and SAR |
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Authors: | Choi Cheol-Hee Kim Joon-Ho Kim Sang-Hyun |
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Institution: | Research Center for Resistant Cells, Chosun University, Gwangju 501-759, Republic of Korea. chchoi@chosun.ac.kr |
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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. |
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Keywords: | Multidrug resistance 5 7 3′ 4′ 5′-Pentamethoxyflavone Flavonoids Chemosensitizer P-glycoprotein Structure-activity relationship |
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