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Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein.

Abstract：

:Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the current study was to investigate different multi-substituted chalcones for their BCRP inhibition. We synthesized chalcones and benzochalcones with different substituents (viz. OH, OCH(3), Cl) on ring A and B of the chalcone structure. All synthesized compounds were tested by Hoechst 33342 accumulation assay to determine inhibitory activity in MCF-7 MX and MDCK cells expressing BCRP. The compounds were also screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity in the calcein AM accumulation assay and were found to be selective towards inhibition of BCRP. Substituents at position 2' and 4' on chalcone ring A were found to be essential for activity; additionally there was a great influence of substituents on ring B. Presence of 3,4-dimethoxy substitution on ring B was found to be optimal, while presence of 2- and 4-chloro substitution also showed a positive effect on BCRP inhibition.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Juvale K,Pape VF,Wiese M

doi

10.1016/j.bmc.2011.10.074

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

346-55

issue

1

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)00901-1

journal_volume

20

pub_type

杂志文章

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