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values below 5 μM. These potent MDR1 inhibitors were found to enhance chemosensitivity to doxorubicin in MDR1-overexpressing cells. The results of the multiple-factor analysis indicated that the 3, 5, and 6-methoxy groups were crucial for enhancing the inhibitory effects on MDR1. Furthermore, the total number of methoxy groups in the flavonol backbone was found to be a significant factor in determining the potency of MDR1 inhibition. These observations provide fundamental insights into the structure-activity relationship between flavonol derivatives and MDR1 inhibition, potentially aiding in overcoming drug resistance in cancer.
Kang et al. (Tue,) studied this question.
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