Optimization of New Catalytic Topoisomerase II Inhibitors as an Anti-Cancer Therapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. In Silico Experiments
2.2. Compounds
2.3. Solubility
2.4. Microsomal Stability Assays
2.5. Microscale Thermophoresis (MST) Assays
2.6. Fluorescence Polarization (FP) Assays
2.7. Other Routine Techniques
2.8. Statistics
3. Results
3.1. Modification of the Scaffold of T60 Using CADD
3.2. T638 Has Improved Solubility and Microsomal Stability in Comparison to T60
3.3. T638 Is an Inhibitor to Both TOP2A and TOP2B
3.4. T638 Is Not a DNA Intercalator but a TOP2 Binder
3.5. T637 and T638 Block TOP2 Proteins from Interacting with DNA
3.6. T637 and T638 Inhibit Cancer Cell Growth and Have Limited Genotoxicity
4. Discussion
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Matias-Barrios, V.M.; Radaeva, M.; Ho, C.-H.; Lee, J.; Adomat, H.; Lallous, N.; Cherkasov, A.; Dong, X. Optimization of New Catalytic Topoisomerase II Inhibitors as an Anti-Cancer Therapy. Cancers 2021, 13, 3675. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13153675
Matias-Barrios VM, Radaeva M, Ho C-H, Lee J, Adomat H, Lallous N, Cherkasov A, Dong X. Optimization of New Catalytic Topoisomerase II Inhibitors as an Anti-Cancer Therapy. Cancers. 2021; 13(15):3675. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13153675
Chicago/Turabian StyleMatias-Barrios, Victor M., Mariia Radaeva, Chia-Hao Ho, Joseph Lee, Hans Adomat, Nada Lallous, Artem Cherkasov, and Xuesen Dong. 2021. "Optimization of New Catalytic Topoisomerase II Inhibitors as an Anti-Cancer Therapy" Cancers 13, no. 15: 3675. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13153675