| dc.description.abstract | ABC transporters are a family of transmembrane proteins that serve multiple physiological functions by pumping unwanted substances out of different cells (efflux).(1) However, some ABC transporters, including Breast Cancer Resistance Protein (BCRP) and Permeability-glycoprotein (P-gp), can be overexpressed by cancer cells and cause multidrug resistance (MDR).(1) The transporters enable the cancer cells to efflux multiple chemotherapeutics and therefore cause treatment failure.(1) Inhibitors for these MDR mediating ABC transporters have been developed but most of them fail in clinical trials because of toxic effects to healthy cells.(2) In this regard, recent research has investigated the potential of flavonoids as BCRP and P-gp inhibitors. Flavonoids are a class of natural polyphenols with little to no toxic effects.(2) In order to identify and develop BCRP/P-gp inhibiting flavonoids, studies have identified structural features (i.e. functional groups) that give flavonoids the highest inhibitory activity.(3–6) For both BCRP and P-gp inhibiting flavonoids some of these beneficial features include: a flavone double bond, absence of hydrogen bond donating groups, and aromatic groups for establishing flavonoid-protein Pi-interactions.(2) This paper presents and discusses additional inhibition enhancing structural features for both BCRP and P-gp and the possibility of combining these results for the identification or development of a dual BCRP/P-gp inhibitor. | |
