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• W4327718174 startingPage "106481" @default.
• W4327718174 abstract "Three series of phenylurea indole derivatives were synthesized with potent inhibitory activities on ABCG2 with simple and efficient synthetic routes. Among these compounds, four phenylurea indole derivatives 3c-3f with extended π system were discovered as the most potent ABCG2 inhibitors, while these compounds showed no inhibition on ABCB1. Compounds 3c and 3f were selected for further investigation to explore the mechanisms of action on reversing ABCG2-mediated multidrug resistance (MDR). The results revealed that compounds 3c and 3f increased the accumulation of mitoxantrone (MX) in ABCG2-overexpressing cells, but they did not alter the expression level or localization of ABCG2 in cells. In addition, both 3c and 3f significantly stimulated the ATP hydrolysis of ABCG2 transporter indicating that they can be competitive substrates of ABCG2 transporter, and thereby increase the accumulation of mitoxantrone in ABCG2-overexpressing H460/MX20 cells. Both 3c and 3f was docked into the drug-binding site of the human ABCG2 transporter protein (PDB 6FFC) with high affinities. This study showed that extending the π system of phenylurea indole derivatives enhanced their inhibitory activities on ABCG2, which may provide a clue for the further research to discover more potent ABCG2 inhibitors." @default.
• W4327718174 created "2023-03-18" @default.
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• W4327718174 date "2023-06-01" @default.
• W4327718174 modified "2023-10-11" @default.
• W4327718174 title "Design, synthesis, and biological evaluation of phenylurea indole derivatives as ABCG2 inhibitors" @default.
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• W4327718174 doi "https://doi.org/10.1016/j.bioorg.2023.106481" @default.
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