TY - JOUR
T1 - Synthesis of methylated quercetin derivatives and their reversal activities on P-gp- and BCRP-mediated multidrug resistance tumour cells
AU - Yuan, Jian
AU - Wong, Iris L K
AU - Jiang, Tao
AU - Wang, Si Wen
AU - Liu, Tao
AU - Jin Wen, Bin
AU - Chow, Ming Cheung
AU - Wan Sheng, Biao
PY - 2012/8/1
Y1 - 2012/8/1
N2 - 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.
AB - 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.
KW - BCRP
KW - Methylated quercetin derivatives
KW - MRP1
KW - Multidrug resistance (MDR)
KW - P-gp
KW - Quercetin
UR - http://www.scopus.com/inward/record.url?scp=84864399172&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2012.05.026
DO - 10.1016/j.ejmech.2012.05.026
M3 - Journal article
C2 - 22743241
SN - 0223-5234
VL - 54
SP - 413
EP - 422
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -