An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent
Abstract
:1. Introduction
2. Results and Discussion
2.1. An Improved Total Synthesis of Neoamphimedine
Human Cancer Cells | Neo IC50 (μM) | Etoposide IC50 (μM) |
---|---|---|
Breast | ||
MCF7 | 0.433 | 0.83 * |
MDA-MB-231 | 0.76 | 9.03 * |
PMC42LA | 0.723 | — |
T47D | 0.740 | 11.58 * |
Colorectal | ||
HCT116 | 0.229 | 1.01 * |
SW48 | 0.006 | 0.87 * |
SW480 | 0.383 | 6.4 ** |
SW620 | 0.060 | 0.39 * |
Leukemia | ||
HEL | 0.135 | 3.88 * |
Kasumi I | 0.244 | 1.32 * |
Molm13 | 0.018 | 0.38 * |
OCI AML3 | 0.036 | — |
Lung | ||
A549 | 0.489 | 3.9 ** |
H2009 | 1.095 | — |
HCC827 | 2.957 | — |
SW1573 | 0.157 | 2.25 * |
2.2. Cytotoxicity Studies with Neo Using a Panel of Human Colorectal Cancer Cell Lines
2.3. Neo Exerts Cytotoxicity by Inducing G2-M Cell Cycle Arrest and Apoptosis
3. Experimental Section
3.1. General Experimental Procedures
3.2. Cell Culture
3.3. Sulforhodamine B (SRB) Cytotoxicity Assay
3.4. SRB Recovery Assay
3.5. Acid Phosphatase (APH) Assay
3.6. FACS Analysis of Cell Cycle Distribution and Apoptosis
3.7. Synthetic Procedures
3.7.1. Methyl 2-hydroxy-5-methoxy-3-nitrobenzoate
3.7.2. Methyl 2,5-Dimethoxy-3-nitrobenzoate (1)
3.7.3. Methyl 3-((2,2-Dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methyl-amino)-2,5-dimethoxy-benzoate (3)
3.7.4. Methyl 1,4-Dihydro-5,8-dimethoxy-4-oxo-quinoline-7-carboxylate (4)
3.7.5. Methyl 5,8-Dimethoxy-4-trifluoromethanesulfonyloxy-quinoline-7-carboxylate (5)
3.7.6. Methyl 4-Bromo-5,8-dimethoxy-quinoline-7-carboxylate (7)
3.7.7. Methyl 5,8-Dimethoxy-4-(2-nitrophenyl)-quinoline-7-carboxylate (6)
3.7.8. 7-[N-(2,2-Dimethoxyethyl)-N-methyl]-carboxamide-5,8-dimethoxy-4-(2-nitrophenyl) quinoline (8)
3.7.9. Neoamphimedine (neo)
4. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Li, L.; Abraham, A.D.; Zhou, Q.; Ali, H.; O'Brien, J.V.; Hamill, B.D.; Arcaroli, J.J.; Messersmith, W.A.; LaBarbera, D.V. An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent. Mar. Drugs 2014, 12, 4833-4850. https://doi.org/10.3390/md12094833
Li L, Abraham AD, Zhou Q, Ali H, O'Brien JV, Hamill BD, Arcaroli JJ, Messersmith WA, LaBarbera DV. An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent. Marine Drugs. 2014; 12(9):4833-4850. https://doi.org/10.3390/md12094833
Chicago/Turabian StyleLi, Linfeng, Adedoyin D. Abraham, Qiong Zhou, Hadi Ali, Jeremy V. O'Brien, Brayden D. Hamill, John J. Arcaroli, Wells A. Messersmith, and Daniel V. LaBarbera. 2014. "An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent" Marine Drugs 12, no. 9: 4833-4850. https://doi.org/10.3390/md12094833