Novel Nonsymmetrical 1,4-Dihydropyridines as Inhibitors of Nonsymmetrical MRP-Efflux Pumps for Anticancer Therapy
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of the 1,4-Dihydropyridines
2.2. MRP Efflux Pump Inhibition of the 1,4-Dihydropyridines
2.3. In Vitro MRP Resistance Studies of Drug Reversal
3. Materials and Methods
3.1. Chemical Reagents and Instruments
3.2. General Procedure for the Synthesis of Compound 3
3.3. General Procedure for the Synthesis of Compounds 4–15
3.4. MRP Inhibition Assay
3.5. MRP Reversal Assay
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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FAR Value a | |||||
---|---|---|---|---|---|
Cpd. | R1 | R2 | MRP1 | MRP2 | Ratio MRP2/MRP1 |
4 | 4-OMe | 3-OMe | 1.07 ± 0.17 | 2.01 ± 0.23 | 1.88 |
5 | 4-OMe | 4-OMe | 0.81 ± 0.15 | 1.40 ± 0.26 | 1.75 |
6 | 4-OMe | 3-Me | 1.16 ± 0.18 | 1.32 ± 0.32 | 1.13 |
7 | 4-OMe | 4-Me | 1.04 ± 0.11 | 1.55 ± 0.34 | 1.49 |
8 | 3-OMe | 3-OMe | 1.35 ± 0.04 | 1.33 ± 0.32 | 0.99 |
9 | 3-OMe | 4-OMe | 1.08 ± 0.13 | 1.59 ± 0.31 | 1.47 |
10 | 3-OMe | 3-Me | 1.12 ± 0.12 | 1.46 ± 0.34 | 1.30 |
11 | 3-OMe | 4-Me | 1.50 ± 0.19 | 1.57 ± 0.31 | 1.05 |
12 | 3,4-OMe | 3-OMe | 1.32 ± 0.13 | 1.48 ± 0.37 | 1.17 |
13 | 3,4-OMe | 4-OMe | 1.31 ± 0.17 | 1.13 ± 0.21 | 0.86 |
14 | 3,4-OMe | 3-Me | 1.17 ± 0.19 | 1.78 ± 0.43 | 1.52 |
15 | 3,4-OMe | 4-Me | 1.00 ± 0.09 | 1.39 ± 0.32 | 1.39 |
Probenecid | 1.23 ± 0.11 | 1.00 ± 0.21 | 0.86 |
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Kreutzer, D.; Ritter, C.A.; Hilgeroth, A. Novel Nonsymmetrical 1,4-Dihydropyridines as Inhibitors of Nonsymmetrical MRP-Efflux Pumps for Anticancer Therapy. Pharmaceuticals 2020, 13, 146. https://doi.org/10.3390/ph13070146
Kreutzer D, Ritter CA, Hilgeroth A. Novel Nonsymmetrical 1,4-Dihydropyridines as Inhibitors of Nonsymmetrical MRP-Efflux Pumps for Anticancer Therapy. Pharmaceuticals. 2020; 13(7):146. https://doi.org/10.3390/ph13070146
Chicago/Turabian StyleKreutzer, David, Christoph A. Ritter, and Andreas Hilgeroth. 2020. "Novel Nonsymmetrical 1,4-Dihydropyridines as Inhibitors of Nonsymmetrical MRP-Efflux Pumps for Anticancer Therapy" Pharmaceuticals 13, no. 7: 146. https://doi.org/10.3390/ph13070146
APA StyleKreutzer, D., Ritter, C. A., & Hilgeroth, A. (2020). Novel Nonsymmetrical 1,4-Dihydropyridines as Inhibitors of Nonsymmetrical MRP-Efflux Pumps for Anticancer Therapy. Pharmaceuticals, 13(7), 146. https://doi.org/10.3390/ph13070146