The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis and Characterization of the Complexes (1)–(3)
2.2. Hydrolysis of the Complexes (1)–(3)
2.3. Interactions of (1) and (2) with Guanosine (Guo)
Sugar Conformation Analysis
2.4. Interactions of (3) with 9-Methyl Guanine (9-MeG)
2.5. Cytotoxic Activity
3. Materials and Methods
3.1. Chemicals
3.2. Methods
3.3. Cell Culture
3.4. Cell Growth Assay
3.5. Determination of Equilibrium Constants
3.6. Determination of Hydrolysis Constants
3.7. Synthesis of the Complexes (1)–(3)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | Pyridine/2-Methylpyridine | en | Guanosine/9-Methylguanine | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
H2 | H3 | H4 | H5 | H6 | CH3 | Ha1a2/b1b2 | H8 | CH3 | H1′ (J1′2′) | H2′ (J2′3′) | H3′ (J3′4′) | H4′ | H5′ (J4′5′) | H5″ (J4′5′’) | |
guo | 8.03 | 5.91 (5.95) | 4.74 (5.40) | 4.41 (3.80) | 4.18 | 3.89 (3.05) | 3.74 (4.05) | ||||||||
[1-D2O] | 8.71 | 7.56 | 8.03 | 7.56 | 8.71 | - | 2.72–2.67 | ||||||||
[1-guo] | 8.66 | 7.52 | 8.00 | 8.66 | 7.52 | - | 2.84–2.80 | 8.44 | 5.89 (4.85) | 4.61 (4.95) | 4.29 (5.60) | 4.21 | 3.86 (2.75) | 3.77 (4.15) | |
[2-D2O] | - | 7.54 | 7.83 | 7.34 | 8.83 | 3.09 | 2.71–2.66 | ||||||||
[2-guo]A | - | 7.48 | 7.87 | 7.39 | 8.93b | 2.96 | 2.82–2.80 | 8.31 | 5.84 (4.70) | 4.58 (4.30) | 4.28 (5.60) | 4.18 | 3.85 (2.75) | 3.74 (4.95) | |
[2-guo]B | - | 7.48 | 7.87 | 7.39b | 8.93b | 2.98 | 2.82–2.80 | 8.29 | 5.84 (4.70) | 4.53 (4.60) | 4.22 (4.90) | 4.18 | 3.85 (2.75) | 3.74 (4.05) | |
9-MeG | 7.76 | 3.65 | |||||||||||||
[2-(9-MeG)] | 7.46 | 7.86 | 7.37 | 8.91 | 2.96 | 2.81 2.79 | 7.99 | 3.58 |
Compound | anti (%) | syn (%) | 3E (%) | 2E (%) | gg (%) | (gt + tg) (%) |
---|---|---|---|---|---|---|
guo | 57 | 43 | 39 | 61 | 59 | 41 |
[1-guo] | 79 | 21 | 54 | 46 | 61 | 39 |
[2-guo]A | 85 | 15 | - | - | 62 | 38 |
[2-guo]B | 93 | 7 | - | - | 53 | 47 |
Pt-N7Gp5′ a | 51 | 49 | 36 | 64 | ||
Me-N7Gp5′ b | 54 | 46 | 97 | 3 | ||
H+-N7Gp5′ a | 57 | 43 | 87 | 13 | ||
Gp5′ a | 36 | 64 | 65 | 35 |
Compound | 2-phpy | 9-MeG | en | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
H3 | H4 | H5 | H6 | H2′ | H3′ | H4′ | H5′ | H6′ | H8 | -CH3 | Ha1a2/b1b2 | |
9-MeG in D2O | 7.76 | 3.58 | ||||||||||
(3) | 7.72 | 8.07 | 7.55 | 8.96 | 8.10 | 7.68 | 7.68 | 7.68 | 8.10 | - | - | 2.41–2.46 |
(3′) | 7.92 | 8.07 | 7.25 | 8.46 | 7.69 | 7.32 | 7.32 | 7.31 | - | - | - | 2.58–2.56 |
[3-(9-MeG)] | 8.23 | 8.15 | 7.65 | 9.12 | 7.64 | 7.44 | 7.44 | 7.44 | 7.64 | 7.21 | 3.62 | 2.60–2.55 |
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Tagari, E.-V.; Sifnaiou, E.; Tsolis, T.; Garoufis, A. The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone. Int. J. Mol. Sci. 2024, 25, 6526. https://doi.org/10.3390/ijms25126526
Tagari E-V, Sifnaiou E, Tsolis T, Garoufis A. The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone. International Journal of Molecular Sciences. 2024; 25(12):6526. https://doi.org/10.3390/ijms25126526
Chicago/Turabian StyleTagari, Evanthia-Vasiliki, Evangelia Sifnaiou, Theodoros Tsolis, and Achilleas Garoufis. 2024. "The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone" International Journal of Molecular Sciences 25, no. 12: 6526. https://doi.org/10.3390/ijms25126526