Synthesis and Cytotoxicity against K562 Cells of 3-O-Angeloyl-20-O-acetyl Ingenol, a Derivative of Ingenol Mebutate
Abstract
:1. Introduction
2. Results
2.1. The Synthesis of 3-O-Angeloyl-20-O-acetyl ingenol (AAI)
2.2. AAI Inhibits Cell Proliferation
2.3. AAI Induces G2/M Phase Arrest, Apoptosis, and Necrosis in K562 Cells
2.4. AAI Disturbs Mitochondrial Membrane Potential (MMP) in K562 Cells
2.5. AAI Modulates Multiple Key Signaling Pathways in K562 Cells
2.6. AAI and Ingenol Mebutate Bind PKCδ in a Similar Manner
3. Discussion
4. Materials and Methods
4.1. Drugs and Reagents
4.2. Gerneral Procedure for the Synthesis of 3-O-Angeloyl-20-O-acetyl ingenol
4.3. Cell Lines and Cell Culture
4.4. Cell Proliferation Inhibition Assay
4.5. Cell Cycle Distribution Assay
4.6. Apoptosis and Necrosis Assay by Annexin V-FITC/PI Double Staining
4.7. MMP Assay
4.8. Western Blotting Assay
4.9. Computational Docking
4.10. MD Simulations
4.11. Binding Energy Calculations
4.12. Data Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Ligand | Free Energy (kcal/mol) | |||||
---|---|---|---|---|---|---|
VDW | EEL | EGB | ESURF | TΔS | ΔG | |
AAI | −30.69 (0.39) | −15.80 (0.68) | 25.14 (0.41) | −3.95 (0.04) | −20.39 (2.86) | −4.91 (2.54) |
ingenol mebutate | −40.51 (0.34) | −19.20 (0.48) | 27.91 (0.27) | −4.46 (0.02) | −20.31 (2.71) | −15.95 (2.31) |
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Liu, M.; Chen, F.; Yu, R.; Zhang, W.; Han, M.; Liu, F.; Wu, J.; Zhao, X.; Miao, J. Synthesis and Cytotoxicity against K562 Cells of 3-O-Angeloyl-20-O-acetyl Ingenol, a Derivative of Ingenol Mebutate. Int. J. Mol. Sci. 2016, 17, 1348. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17081348
Liu M, Chen F, Yu R, Zhang W, Han M, Liu F, Wu J, Zhao X, Miao J. Synthesis and Cytotoxicity against K562 Cells of 3-O-Angeloyl-20-O-acetyl Ingenol, a Derivative of Ingenol Mebutate. International Journal of Molecular Sciences. 2016; 17(8):1348. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17081348
Chicago/Turabian StyleLiu, Ming, Fangling Chen, Rilei Yu, Weiyi Zhang, Mei Han, Fei Liu, Jing Wu, Xingzeng Zhao, and Jinlai Miao. 2016. "Synthesis and Cytotoxicity against K562 Cells of 3-O-Angeloyl-20-O-acetyl Ingenol, a Derivative of Ingenol Mebutate" International Journal of Molecular Sciences 17, no. 8: 1348. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17081348