Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Physical Measurements
2.2. Synthesis of Iridium(III) Complexes
2.2.1. Synthesis of [Ir(Hppy)2(NP)]PF6 (1)
2.2.2. Synthesis of [Ir(Hppy)2(NAP)]PF6 (2)
2.2.3. Synthesis of [Ir(Hppy)2(DAP)]PF6 (3)
2.3. Cell Culture
2.4. Oil–Water Partition Coefficient Determination
2.5. Cell Uptake
2.6. In Vitro Cytotoxicity Assay
2.7. Colony-Forming Assay
2.8. Analysis of Cell Invasion
2.9. Comet Assay
2.10. Apoptosis Analyses
2.11. Measurement of Reactive Oxygen Species
2.12. Determination of Intracellular Ca2+ Levels
2.13. Localization at the Mitochondria of the Complexes
2.14. Mitochondrial Membrane Potential Assay (∆Ψm)
2.15. ATP Quantification Assay
2.16. Cell Cycle Assay
2.17. Western Blot Analysis
3. Results and Discussion
3.1. Synthesis and Characterization
3.2. Determination of Lipophilicity
3.3. Cellular Uptake
3.4. Cytotoxic Activity In Vitro
3.5. Inhibition of Colony Formation
3.6. Transwell Migration Assay
3.7. Comet Assay
3.8. Apoptosis Studies
3.9. Iridium(III) Complexes Prompt ROS Production
3.10. Detection of Intracellular Ca2+ Levels
3.11. Cellular Localization and Mitochondrial Damage Analysis
3.12. Determination of ATP
3.13. Cell Cycle Distribution
3.14. Western Blot Analysis
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 1, 2 and 3 are available from the authors. |
Complex | SGC-7901 | A549 | HeLa | Eca-109 | HepG2 | BEL-7402 | NIH 3T3 | logPo/w |
---|---|---|---|---|---|---|---|---|
NP | 18.4 ± 0.1 | 11.1 ± 0.7 | 18.1 ± 1.7 | ND | 16.7 ± 0.5 | 23.5 ± 1.1 | >200 | ND |
NAP | 90.9 ± 7.4 | 42.7 ± 2.1 | 45.8 ± 4.0 | ND | 56.0 ± 1.9 | 21.1 ± 0.8 | 61.9 ± 1.9 | ND |
DAP | 15.8 ± 2.8 | 5.0 ± 0.3 | 9.2 ± 1.0 | ND | 4.6 ± 0.8 | 37.4 ± 3.2 | 12.3 ± 0.8 | ND |
[Ir(Hppy)2Cl]2 | 3.5 ± 0.1 | 3.3 ± 0.4 | 2.5 ± 0.2 | ND | 5.5 ± 0.3 | 8.4 ± 0.4 | 6.3 ± 0.3 | ND |
1 | 3.6 ± 0.1 | 14.3 ± 2.4 | 16.3 ± 0.9 | 20.3 ± 0.9 | 30.9 ± 0.7 | 23.0 ± 0.8 | 14.6 ± 1.3 | 1.01 |
2 | 14.1 ± 0.5 | 80.6 ± 1.4 | 52.6 ± 1.4 | 72.6 ± 5.3 | 99 ± 14.7 | 68.7 ± 1.5 | 23.0 ± 1.5 | 1.33 |
3 | 11.1 ± 1.3 | >100 | 59.7 ± 6.8 | 97.1 ± 0.2 | 95.0 ± 9.1 | 68.8 ± 4.6 | >100 | 0.78 |
Cisplatin | 3.6 ± 0.5 | 7.5 ± 1.3 | 7.0 ± 1.0 | 11.2 ± 0.6 | 12.5 ± 1.5 | 10.8 ± 1.6 | ND | ND |
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Zhang, L.-X.; Gu, Y.-Y.; Wang, Y.-J.; Bai, L.; Du, F.; Zhang, W.-Y.; He, M.; Liu, Y.-J.; Chen, Y.-Z. Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells. Molecules 2019, 24, 3129. https://doi.org/10.3390/molecules24173129
Zhang L-X, Gu Y-Y, Wang Y-J, Bai L, Du F, Zhang W-Y, He M, Liu Y-J, Chen Y-Z. Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells. Molecules. 2019; 24(17):3129. https://doi.org/10.3390/molecules24173129
Chicago/Turabian StyleZhang, Li-Xia, Yi-Ying Gu, Yang-Jie Wang, Lan Bai, Fan Du, Wen-Yao Zhang, Miao He, Yun-Jun Liu, and Yan-Zhong Chen. 2019. "Design, Synthesis, and Anticancer Effect Studies of Iridium(III) Polypyridyl Complexes against SGC-7901 Cells" Molecules 24, no. 17: 3129. https://doi.org/10.3390/molecules24173129