Halogenated Chalcones with High-Affinity Binding to P-Glycoprotein: Potential Modulators of Multidrug Resistance
- 19 September 1998
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 41 (21), 4161-4164
- https://doi.org/10.1021/jm9810194
Abstract
Previous studies have shown that flavonoids are modulators of the transmembrane P-glycoprotein (P-gp) which mediates cell multidrug resistance. Some structural elements have been identified which seem to contribute to these compounds' activity. In the present study, a series of halogenated chalcones was prepared to further explore the structural requirements for the P-gp modulation. Four halogenated chalcones have been synthesized and evaluated as potential modulators of P-gp-mediated multidrug resistance of cancer cells by in vitro assays using a purified recombinant domain of the transporter containing the modulator binding site. Halogenated chalcones exhibited high-affinity binding, the 2‘,4‘,6‘-trihydroxy-4-iodochalcone behaving as the most potent compound with a KD value in the nanomolar range.Keywords
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