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• W3197906265 startingPage "113795" @default.
• W3197906265 abstract "P-glycoprotein (P-gp; ABCB1)-mediated drug efflux causes multidrug resistance in cancer. Previous synthetic methylated epigallocatechin (EGC) possessed promising P-gp modulating activity. In order to further improve the potency, we have synthesized some novel stereoisomers of methylated epigallocatechin (EGC) and gallocatechin (GC) as well as epicatechin (EC) and catechin (C). The (2R, 3S)-trans-methylated C derivative 25 and the (2R, 3R)-cis-methylated EC derivative 31, both containing dimethyoxylation at ring B, tri-methoxylation at ring D and oxycarbonylphenylcarbamoyl linker between ring D and C3, are the most potent in reversing P-gp mediated drug resistance with EC50 ranged from 32 nM to 93 nM. They are non-toxic to fibroblast with IC50 > 100 μM. They can inhibit the P-gp mediated drug efflux and restore the intracellular drug concentration to a cytotoxic level. They do not downregulate surface P-gp protein level to enhance drug retention. They are specific for P-gp with no or low modulating activity towards MRP1- or BCRP-mediated drug resistance. In summary, methylated C 25 and EC 31 derivatives represent a new class of potent, specific and non-toxic P-gp modulator." @default.
• W3197906265 created "2021-09-13" @default.
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• W3197906265 date "2021-12-01" @default.
• W3197906265 modified "2023-10-01" @default.
• W3197906265 title "Synthesis and evaluation of stereoisomers of methylated catechin and epigallocatechin derivatives on modulating P-glycoprotein-mediated multidrug resistance in cancers" @default.
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• W3197906265 doi "https://doi.org/10.1016/j.ejmech.2021.113795" @default.
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