10.1002/cmdc.201200154
The research focuses on the development of potent and highly selective inhibitors of the breast cancer resistance protein (ABCG2), a key factor in multidrug resistance in cancer cells. The study reports a one-step synthesis method for 6-halogenochromones linked to a tryptamine unit, which were evaluated for their inhibitory activity against ABCG2. The synthesis involved coupling 6-substituted-4-oxo-4H-chromene-2-carboxylic acid with tryptamine using bis(2-oxo-3-oxazolidinyl)phosphonic chloride (BOP-Cl) as the coupling agent. The synthesized compounds were screened for their effects on the inhibition of mitoxantrone efflux in ABCG2-transfected HEK293 cells, using flow cytometry. The most active compounds were further tested for selectivity against P-gp/ABCB1 and MRP1/ABCC1 transporters and evaluated for their cytotoxicity and ability to chemosensitize cancer cells to anticancer drugs like mitoxantrone and SN-38. The experiments included assays for drug transport, cytotoxicity, and sensitization to anticancer drugs, with analyses performed using flow cytometry and MTT colorimetric assays.
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