Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein)

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Hong-May SimMei-Lin Go

Abstract

A series of 4,6-dimethoxyaurones were synthesized by reacting 4,6-dimethoxybenzofuran-3(2H)-one with various benzaldehydes in a base-catalyzed aldol reaction. A Z configuration was assigned to the aurones based on spectroscopic and crystallographic data. The aurones were tested for their ability to modulate ABCG2 (breast cancer resistance protein)-mediated multidrug resistance in vitro. Several members (0.5 microM) increased the accumulation of mitoxantrone (MX) in human breast cancer cells (MDA-MB-231) transfected with ABCG2 and re-sensitized these cells to the cytotoxic effects of MX. In the re-sensitization assay, aurones at 0.5 microM reduced the resistance of the transfected cells to MX to just twice that of the parental cells, exceeding fumitremorgin C (FTC) tested at the same concentration. The aurones (10 microM) also increased calcein-AM accumulation in MDCKII/MDR1 cells that were transfected with ABCB1 (P-glycoprotein), at levels comparable to verapamil tested at the same concentration. Structure-activity analysis showed that substitution of the benzylidene ring B of the aurone template was less important for ABCG2 inhibition, with little variation in activity noted for compounds with an unsubstituted ring B or one th...Continue Reading

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Citations

Jul 15, 2011·Acta Crystallographica. Section E, Structure Reports Online·J Satyanarayana ReddyK Anand Solomon
Jan 6, 2012·Acta Crystallographica. Section E, Structure Reports Online·J Satyanarayana ReddyK Anand Solomon
May 13, 2014·European Journal of Medicinal Chemistry·Marta P CarrascoRui Moreira
Jan 1, 2012·International Journal of Medicinal Chemistry·Marina RoussakiAnastasia Detsi
Apr 10, 2015·Marine Drugs·Lilia CherigoSergio Martinez-Luis
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Jul 10, 2020·Bioscience, Biotechnology, and Biochemistry·Hiroki KobayashiMinoru Yoshida

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