Recent advances in the discovery of flavonoids and analogs with high-affinity binding to P-glycoprotein responsible for cancer cell multidrug resistance

✍ Scribed by Ahcène Boumendjel; Attilio Di Pietro; Charles Dumontet; Denis Barron

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 189 KB
• Volume: 22
• Category: Article
• ISSN: 0198-6325
• DOI: 10.1002/med.10015

✦ Synopsis

P-glycoprotein (P-gp) is a plasma membrane glycoprotein that confers multidrug resistance on cells by virtue of its ability to exclude cytotoxic drugs in an ATP-dependent manner. The most commonly considered hypothesis is that P-gp acts as an ATP-driven drug-export pump, the mechanism of which is not understood in detail. Therefore, a tremendous effort is being made to find out modulator molecules to inhibit P-gp. We have been developing flavonoid derivatives as a new class of promising modulators using a new in vitro rational-screening assay based on measurements of the binding-affinity toward the C-terminal nucleotide-binding domain (NBD2) of P-gp. This review is focused on our results obtained with a variety of flavonoids. Structure-activity relationships of flavonoids as potential MDR modulators are reported.