Aurones as Modulators of ABCG2 and ABCB1: Synthesis and Structure-Activity Relationships.

Summary of "Aurones as Modulators of ABCG2 and ABCB1: Synthesis and Structure-Activity Relationships."

The ability of aurones to modulate the efflux activities of ABCG2 and ABCB1 was investigated by quantifying their effects on the accumulation of pheophorbide A (PhA) in ABCG2-overexpressing MDA-MB-231/R cells and calcein AM in ABCB1-overexpressing MDCKII/MDR1 cells. Key structural features for interactions at both ABCG2 and ABCB1 are a methoxylated ring A, an intact exocyclic double bond, and the location of the carbonyl bond on ring C. Modifications on rings B and C were less critical and served primarily to moderate activity and selectivity for one or both transporters. These SAR trends were quantified by Free-Wilson analyses and are reflected in a pharmacophore model for PhA accumulation. Several compounds were found to be equipotent with fumitremorgin C (FTC) in promoting PhA accumulation, and they also demonstrated strong affinities for ABCB1. These compounds were disubstituted on ring B with methoxy or a combination of methoxy and hydroxy groups. Taken together, our findings highlight the versatility of the aurone template as a lead scaffold for the design of dual-targeting ABCG2 and ABCB1 modulators.


Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543 (Singapore), Fax: (+65) 6779-1554.

Journal Details

This article was published in the following journal.

Name: ChemMedChem
ISSN: 1860-7187
Pages: 713-24


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