Kim, Mi Kyoung Choo, Hyunah Chong, Youhoon 2024-01-20T09:01:20Z 2024-01-20T09:01:20Z 2021-09-02 2014-09-11 0022-2623 https://pubs.kist.re.kr/handle/201004/126354 Quercetinamino acid conjugates with alanine or glutamic acid moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects were evaluated. A quercetinglutamic acid conjugate, 7-O-Glu-Q (3a), was as potent as verapamil in reversing MDR and sensitized MDR MES-SA/Dx5 cells to various anticancer drugs with EC50 values of 0.80.9 mu M. Analysis on Rh-123 accumulation confirmed that 3a inhibits drug efflux by Pgp, and Pgp ATPase assay showed that 3a interacts with the drug-binding site of Pgp to stimulate its ATPase activity. Physicochemical analysis of 3a revealed that solubility, stability, and cellular uptake of quercetin were significantly improved by the glutamic acid promoiety, which eventually dissociates from 3a to produce quercetin and quercetin metabolites in intracellular milieu. Taken together, potent MDR-modulating activity along with intracellular conversion into the natural flavonoid quercetin warrants development of the quercetinamino acid conjugates as safe MDR modulators. English AMER CHEMICAL SOC CANCER CELL-LINE IN-VITRO FLAVONOID DIMERS APIGENIN HOMODIMERS BIVALENT MODULATORS PROTEIN-KINASES HYDROXYL-GROUPS FLOW-CYTOMETRY CYCLOSPORINE-A REVERSAL Water-Soluble and Cleavable Quercetin-Amino Acid Conjugates as Safe Modulators for P-Glycoprotein-Based Multidrug Resistance Article 10.1021/jm500290c 1 JOURNAL OF MEDICINAL CHEMISTRY, v.57, no.17, pp.7216 - 7233 JOURNAL OF MEDICINAL CHEMISTRY 57 17 7216 7233 scie scopus 000341619400005 2-s2.0-84907195320 Chemistry, Medicinal Pharmacology & Pharmacy Article CANCER CELL-LINE IN-VITRO FLAVONOID DIMERS APIGENIN HOMODIMERS BIVALENT MODULATORS PROTEIN-KINASES HYDROXYL-GROUPS FLOW-CYTOMETRY CYCLOSPORINE-A REVERSAL Quercetin-amino acid conjugate P-glycoprotein multidrug resistance water-soluble