Pena-Solorzano, Diana and Scholler, Matthias and Bernhardt, Guenther and Buschauer, Armin and Koenig, Burkhard and Ochoa-Puentes, Cristian (2018) Tariquidar-Related Chalcones and Ketones as ABCG2 Modulators. ACS MEDICINAL CHEMISTRY LETTERS, 9 (8). pp. 854-859. ISSN 1948-5875,
Full text not available from this repository. (Request a copy)Abstract
ABC transporters, including ABCG2, play a vital role in defending the human body against the vast range of xenobiotics. Even though this is beneficial for human health, these protein transporters have been implicated in the emerging resistance of cancer cells to a variety of structurally and functionally diverse anticancer drugs. In order to investigate their role in resistance, potent and selective ABCG2 modulators have been described in the literature. A leading class of modulators are the tariquidar analogues; however, their susceptibility to hydrolysis limits their applicable use. To overcome this, we synthesized a novel series of chalcone- and ketone-based compounds inspired by reported tariquidar analogues. Compounds were characterized and evaluated for their ABCG2 modulatory activity and ABC transporter selectivity. When compared to transporters ABCB1 and ABCC1, the chalcone-based compounds exhibited selectivity for ABCG2, while the ketone-based compounds showed only a slight preference for ABCG2. From the former series, chalcone 16d (UR-DP48) displayed similar activity to the reference fumitremorgin C, both producing comparable maximal effects. The compound exhibited marked antiproliferative activity, while cytotoxicity was less pronounced for the most active compound 17f from the ketone series. Chalcone-containing tariquidar analogues are promising modulators to aid in functional investigations of ABCG2 transporters.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CANCER RESISTANCE PROTEIN; MULTIDRUG TRANSPORTER ABCG2; P-GLYCOPROTEIN; INHIBITORS; POLYSPECIFICITY; CYTOTOXICITY; REVERSAL; Tariquidar; chalcone; ketone; ABCG2; modulator |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2020 12:40 |
| Last Modified: | 11 Mar 2020 12:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14094 |
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