Piperazinobenzopyranones and Phenalkylaminobenzopyranones: Potent Inhibitors of Breast Cancer Resistance Protein (ABCG2)

Ahcene Boumendjel 1 Edwige Nicolle 1 Thomas Moraux 2 Bastien Gerby 3 Madeleine Blanc Xavier Ronot 4 Jean Boutonnat 5
4 EPHE
TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
5 RFMQ
TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
Abstract : In continuing research that led us to identify chromanone derivatives (J. Med. Chem. 2003, 46, 2125) as P-glycoprotein inhibitors, we obtained analogues able to modulate multidrug resistance (MDR) mediated by the breast cancer resistance protein (BCRP). The linkage of 5-hydroxybenzopyran-4-one to piperazines or phenalkylamines affords highly potent inhibitors of BCRP. By using sensitive (HCT116) and resistant colon cancer cells expressing BCRP, we evaluated the effect of 14 benzopyranone (chromone) derivatives on the accumulation and the cytotoxic effect of the anticancer drug, mitoxantrone. At 10 microM, three compounds increased both intracellular accumulation and cytotoxicity of mitoxantrone in HCT116/R cells with a comparable rate as fumitremorgin C and Gleevec used as reference inhibitors. The most potent molecules 5b and 5c are still active at 1 microM, whereas FTC shows weak inhibition. These molecules do not induce cell death as shown by the cell cycle distribution study, which makes them potential candidates for in vivo studies.
Document type :
Journal articles
Complete list of metadatas

https://hal.archives-ouvertes.fr/hal-02353671
Contributor : Bastien Gerby <>
Submitted on : Thursday, November 7, 2019 - 1:53:35 PM
Last modification on : Friday, November 8, 2019 - 9:54:42 PM

Links full text

Identifiers

Citation

Ahcene Boumendjel, Edwige Nicolle, Thomas Moraux, Bastien Gerby, Madeleine Blanc, et al.. Piperazinobenzopyranones and Phenalkylaminobenzopyranones: Potent Inhibitors of Breast Cancer Resistance Protein (ABCG2). Journal of Medicinal Chemistry, American Chemical Society, 2005, 48 (23), pp.7275-7281. ⟨10.1021/jm050705h⟩. ⟨hal-02353671⟩

Share

Metrics

Record views

12