title: Synthesis of methylated quercetin derivatives and their reversal activities on P-gp- and BCRP-mediated multidrug resistance tumour cells.
abstract: Three methylated quercetins and a series of O-3 substituted 5,7,3',4'-tetra-O-methylated quercetin derivatives have been synthesized and evaluated on the modulating activity of P-gp, BCRP and MRP1 in cancer cell lines. Compound 17 (with a 2-((4-methoxybenzoyl)oxy)ethyl at O-3) is the most potent P-gp modulator. Three derivatives, compound 9 (3,7,3',4'-tetra-O-methylated quercetin), compound 14 (with a 2-((3-oxo-3-(3,4,5trimethoxyphenyl)prop-1-en-1-yl)oxy)ethyl at O-3) and compound 17, consistently exhibited promising BCRP-modulating activity. Interestingly, compound 17 was found to be equipotent against both P-gp and BCRP. Importantly, these synthetic quercetin derivatives did not exhibit any inherent cytotoxicity to cancer cell lines or normal mouse fibroblast cell lines. These quercetin derivatives can be employed as safe and effective modulators of P-gp- or BCRP-mediated drug resistance in cancer.
authors: Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors: Jian
authors: J
authors: Yuan
authors: Iris L K
authors: IL
authors: Wong
authors: Tao
authors: T
authors: Jiang
authors: Si Wen
authors: SW
authors: Wang
authors: Tao
authors: T
authors: Liu
authors: Bin Jin
authors: BJ
authors: Wen
authors: Larry M C
authors: LM
authors: Chow
authors: Biao
authors: B
authors: Wan Sheng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D008745:Methylation; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D011794:Quercetin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011794:Quercetin; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1