Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein)

Aurones as Modulators of ABCG2 and ABCB1: Synthesis and Structure–Activity Relationships

“…[22] However, only a limited number of compounds were evaluated in that study because of the low-throughput nature of the assay. In view of the potential of the aurone as a lead for developing potent, nontoxic modulators of clinically important ABC transport proteins, it is important to gain an understanding of the structural requirements for the aurone-ABCG2 interaction and to determine if these requirements are aligned with those necessary for interaction with another clinically important transport protein, ABCB1.…”

“…[22] Aurones resensitized ABCG2-overexpressing cancer cells to mitoxantrone (an antiThe ability of aurones to modulate the efflux activities of ABCG2 and ABCB1 was investigated by quantifying their effects on the accumulation of pheophorbide A (PhA) in ABCG2-overexpressing MDA-MB-231/R cells and calcein AM in ABCB1-overexpressing MDCKII/MDR1 cells. Key structural features for interactions at both ABCG2 and ABCB1 are a methoxylated ring A, an intact exocyclic double bond, and the location of the carbonyl bond on ring C. Modifications on rings B and C were less critical and served primarily to moderate activity and selectivity for one or both transporters.…”

Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR

“…The chemical shift of the olefinic (b) proton is deshielded in the E isomer of aurones and appears downfield (ca 7.01 ppm) compared to the Z isomer (ca 6.70 ppm) [29,32]. Both 1 H and 13 C NMR data of Series 1e5 supported the assignment of Z-stereochemistry and this was further confirmed by the x-ray structures of 1-10 and 3-10 which showed the presence of the exocyclic double bond in the thermodynamically more stable Z configuration [33,34].…”

“…General procedure for the synthesis of series 1 3,5-Dimethoxyphenoxyacetic acid (1-28) and 4,6-dimethoxybenzofuran-3(2H)-one (1-27) were synthesized as described earlier [25,34]. To a solution of 1-27 (100 mg, 0.52 mmol) in methanol (10 ml) was added the substituted benzaldehyde (0.76 mmol), followed by a solution of KOH (500 mg, 8.92 mmol) in distilled water (1 ml).…”

Therapeutic strategies to eliminate breast cancer stem cells

“…For example, new studies may focus on different end points, such as rates of tumor recurrence, instead of reduction in tumor size. Furthermore, new inhibitors are being developed that target the ABCG2 transporter, which is the subtype most commonly expressed on CSC [43].…”