Ochoa-Puentes, Cristian and Bauer, Stefanie and Kuehnle, Matthias and Bernhard, Guenther and Buschauer, Armin and Koenig, Burkhard (2013) Benzanilide-Biphenyl Replacement: A Bioisosteric Approach to Quinoline Carboxamide-Type ABCG2 Modulators. ACS MEDICINAL CHEMISTRY LETTERS, 4 (4). pp. 393-396. ISSN 1948-5875,
Full text not available from this repository. (Request a copy)Abstract
Recently reported compounds such as UR-COP78 (6) are among the most potent and selective ABCG2 modulators known so far but are prone to rapid enzymatic cleavage at the central benzanilide moiety. In search for more stable analogues, according to a bioisosteric approach, a series of N-(biphenyl-3-yl)quinoline carboxamides was prepared by solid phase and solution phase synthesis. The biphenyl moiety was constructed by Suzuki coupling. Inhibition of ABCB1 and ABCG2 was determined in a calcein-AM and a Hoechst 33342 microplate assay, respectively. Most synthesized compounds selectively inhibited the ABCG2 transporter at submicromolar concentrations with a maximal inhibitory effect (I.) over 90% (e.g., UR-COP228 (22a), IC50 591 nM, I-max 109%; UR-COP258 (31), IC50 544 nM, I-max 112%), though with lower potency and selectivity than 6. The biphenyl analogues are considerably more stable and demonstrate that the benzanilide core is not a crucial structural feature of quinoline carboxamide-type ABCG2 modulators.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CANCER RESISTANCE PROTEIN; MULTIDRUG-RESISTANCE; FUMITREMORGIN-C; P-GLYCOPROTEIN; IN-VITRO; TRANSPORTER; PACLITAXEL; INHIBITION; TARIQUIDAR; ABC transporter; breast cancer resistance protein; MCF-7 cells; solid phase synthesis; Suzuki coupling |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| 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: | 17 Apr 2020 09:20 |
| Last Modified: | 17 Apr 2020 09:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16891 |
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