Tyrosine–Chlorambucil Conjugates Facilitate Cellular Uptake through L-Type Amino Acid Transporter 1 (LAT1) in Human Breast Cancer Cell Line MCF-7
Abstract
:1. Introduction
2. Results
2.1. Synthesis of Chlorambucil Derivatives
2.2. In Vitro Conversion
2.3. LAT1 Binding Affinity
2.4. In Vitro Cellular Uptake
2.5. Antiproliferative Activity
3. Discussion
4. Materials and Methods
4.1. General Synthetic Procedure
4.2. HPLC Analysis
4.3. In Vitro Conversion
4.4. Cell Line and Culture Condition
4.5. LAT1 Binding Affinity
4.6. In Vitro Cellular Uptake
4.7. Antiproliferative Activity
4.8. Computational Analysis
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Computational Parameter | Compound | ||
---|---|---|---|
Chlorambucil | 1 | 2 | |
Log P | 4.1 | 4.7 | 4.1 |
Molecular weight (g/mol) | 304.2 | 467.4 | 466.4 |
Molecular accessible area (Å2) | 558.3 | 798.7 | 802.6 |
Polar surface area (Å2) | 40.5 | 92.8 | 95.7 |
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Pocasap, P.; Weerapreeyakul, N.; Timonen, J.; Järvinen, J.; Leppänen, J.; Kärkkäinen, J.; Rautio, J. Tyrosine–Chlorambucil Conjugates Facilitate Cellular Uptake through L-Type Amino Acid Transporter 1 (LAT1) in Human Breast Cancer Cell Line MCF-7. Int. J. Mol. Sci. 2020, 21, 2132. https://doi.org/10.3390/ijms21062132
Pocasap P, Weerapreeyakul N, Timonen J, Järvinen J, Leppänen J, Kärkkäinen J, Rautio J. Tyrosine–Chlorambucil Conjugates Facilitate Cellular Uptake through L-Type Amino Acid Transporter 1 (LAT1) in Human Breast Cancer Cell Line MCF-7. International Journal of Molecular Sciences. 2020; 21(6):2132. https://doi.org/10.3390/ijms21062132
Chicago/Turabian StylePocasap, Piman, Natthida Weerapreeyakul, Juri Timonen, Juulia Järvinen, Jukka Leppänen, Jussi Kärkkäinen, and Jarkko Rautio. 2020. "Tyrosine–Chlorambucil Conjugates Facilitate Cellular Uptake through L-Type Amino Acid Transporter 1 (LAT1) in Human Breast Cancer Cell Line MCF-7" International Journal of Molecular Sciences 21, no. 6: 2132. https://doi.org/10.3390/ijms21062132