Obreque-Balboa, Jose Esteban and Sun, Qiu and Bernhardt, Guenther and Koenig, Burkhard and Buschauer, Armin (2016) Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 109. pp. 124-133. ISSN 0223-5234, 1768-3254
Full text not available from this repository. (Request a copy)Abstract
A series of chromones, bearing substituted amino groups or N-substituted carboxamide moieties in position 2, was synthesized and characterized in cellular assays for modulation of the ABC transporters ABCC1 (MDCKII-MRP1 cells), ABCB1 (Kb-V1 cells) and ABCG2 (MCF-7/Topo cells). The most potent ABCC1 modulators identified among these flavonoid-type compounds were comparable to the reference compound reversan regarding potency, but superior in terms of selectivity concerning ABCB1 and ABCG2 (2-[4-(Benzo[c][1,2,5]oxadiazol-5-ylmethyl)piperazin-1-yl]-5,7-dimethoxy-4H-chromen-4-one (51): ABCC1, IC50 11.3 mu M; inactive at ABCB1 and ABCG2). Compound 51 was as effective as reversan in reverting ABCC1-mediated resistance to cytostatics in MDCKII-MRP1 cells and proved to be stable in mouse plasma and cell culture medium. Modulators, such as compound 51, are of potential value as pharmacological tools for the investigation of the (patho)physiological role of ABCC1. (C) 2015 Elsevier Masson SAS. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RESISTANCE-ASSOCIATED PROTEIN-1; MEDIATED MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; BIOLOGICAL EVALUATION; ABCG2 MODULATORS; CELL-LINE; MRP1; TRANSPORTER; INHIBITORS; CANCER; ABC transporter; Multidrug resistance; Chromone; Reversan; ABCC1; MRP1 |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2019 09:13 |
| Last Modified: | 12 Mar 2019 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2400 |
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