Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Chemical Characterisation
2.3. Biophysical Characterisation
3. Materials and Methods
3.1. Materials
3.2. Synthesis
3.2.1. Synthesis of [Pt(PyPy)(Cl)2] (1), [Pt(ImPy)(Cl)2] (2) and [Pt(BImPy)(Cl)2] (3)
3.2.2. Synthesis of [Pt(DACH)(PyPy)]2+ (4a/b), [Pt(DACH)(ImPy)]2+ (5a/b), [Pt(DACH)(BImPy)]2+ (6a/b) Complexes
3.3. Cytotoxicity Methodology
3.4. Biophysical Characterization
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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Complex | Molecular Formula | Yield (%) | ESI-MS (m/z) [M]2+ Calc. (Found) | Lipophilicity | UV/λmax (nm) (ε/mol−1·dm3·cm−1) × 102 |
---|---|---|---|---|---|
4a | C15H25N4PtCl2 | 99 | 228.01 (228.59) | 2.68 ± 0.02 | 245 (243), 268 (230) |
4b | C15H25N4PtCl2 | 98 | 228.01 (228.09) | 2.65 ± 0.02 | 207(42.6), 249 (3.37) |
5a | C14H21N5PtCl2 | 99 | 227.07 (227.58) | 2.50 ± 0.02 | 266 (112), 331 (56.6) |
5b | C14H21N5PtCl2 | 95 | 227.07 (227.08) | 2.26 ± 0.02 | 203 (389), 267 (113) |
6a | C18H23N5PtCl2 | 95 | 252.08 (252.08) | 2.42 ± 0.02 | 205 (674), 330(178) |
6b | C18H23N5PtCl2 | 97 | 252.08 (252.08) | 2.46 ± 0.025 | 205 (656), 330 (186) |
Complex | Binding Stoichiometry | ΔFsat | Ka × 104 | n | KF × 103 | Kq × 103 | KSV × 103 |
---|---|---|---|---|---|---|---|
1 | 3.61 | 99.1 | 5.05 | 0.91 | 2.69 | 0.40 | 1.65 |
2 | 3.82 | 80.9 | 2.75 | 1.18 | 3.12 | 0.50 | 1.68 |
3 | 3.40 | 110.3 | 5.10 | 1.24 | 3.72 | 0.51 | 2.18 |
4a | 1.48 | 135.0 | 1.06 | 1.83 | 6.20 | 0.83 | 4.16 |
4b | 1.17 | 121.0 | 1.40 | 1.68 | 5.77 | 0.74 | 3.85 |
5a | 0.80 | 122.4 | 5.89 | 0.87 | 3.16 | 0.36 | 2.11 |
5b | 0.78 | 165.9 | 3.15 | 0.95 | 3.66 | 0.41 | 2.54 |
6a | 0.84 | 116.7 | 0.66 | 0.71 | 2.94 | 0.30 | 2.12 |
6b | 0.94 | 113.0 | 7.43 | 0.67 | 2.84 | 0.30 | 2.07 |
Complex | Cell Line | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
HT29 | U87 | MCF-7 | H460 | A431 | Du145 | BE2-C | SJ-G2 | MIA | MCF10A | SI | |
Colon | Glioblastoma | Breast | Lung | Skin | Prostate | Neuroblastoma | Glioblastoma | Pancreas | Breast (Normal) | MCF10A/ MCF-7 | |
1 | 53 ± 1.0 | 36 ± 1.5 | 30 ± 1.0 | 16 ± 1.7 | >50 | >50 | >50 | >50 | >50 | >50 | 0.97 |
2 | 34 ± 2.0 | 30 ± 2.0 | 25 ± 2.3 | 4 ± 1.0 | 42 ± 3.5 | 36 ± 1.3 | 37 ± 4.0 | 14.0 ± 0.17 | 29 ± 2.3 | 13.0 ± 0.6 | 0.57 |
3 | >50 | 37 ± 2.0 | 12 ± 1.2 | 15± 3.1 | 47 ± 2.5 | >50 | >50 | 42 ± 1.5 | >50 | 45 ± 3.2 | 2.08 |
4a | >50 | 48 ± 2.6 | 3.2 ± 0.6 | 4.4 ± 0.7 | 9 ± 2.3 | 47 ± 1.7 | 37.5 ± 0.5 | 17 ± 1.9 | 12 ± 1.0 | 42 ± 3.0 | 4.69 |
4b | >50 | 43.0 ± 0.67 | 12.50 ± 0.76 | 31.00 ± 0.88 | 30.0 ± 4.7 | >50 | 31 ± 1.20 | >50 | 43 ± 1.0 | 45 ± 0.0 | 1.44 |
5a | 0.56 ± 0.1 | 0.036 ± 0.009 | 0.15 ± 0.03 | 0.29 ± 0.05 | 0.37 ± 0.06 | 0.29 ± 0.07 | 0.21 ± 0.04 | 2.70 ± 0.46 | 0.43 ± 0.07 | 0.15 ± 0.03 | 0.87 |
5b | 0.75 ± 0.07 | 0.05 ± 0.01 | 0.30 ± 0.07 | 0.37 ± 0.05 | 0.49 ± 0.07 | 0.44 ± 0.07 | 0.30 ± 0.05 | 4.5 ± 0.6 | 0.56 ± 0.11 | 0.22 ± 0.03 | 0.5 |
6a | 0.45 ± 0.02 | 0.034 ± 0.003 | 0.16 ± 0.03 | 0.26 ± 0.04 | 0.36 ± 0.05 | 0.30 ± 0.04 | 0.19 ± 0.02 | 2.70 ± 0.29 | 0.30 ± 0.03 | 0.15 ± 0.01 | 0.53 |
6b | 33 ± 1.2 | 7.6 ± 0.46 | 8 ± 1.6 | 16± 1.2 | 24 ± 2.6 | 22 ± 1.5 | 30 ± 2.1 | 38 ± 5.9 | 30 ± 6.9 | 17 ± 1.5 | 1.57 |
Cisplatin | 11 ± 1.9 | 4 ± 1.1 | 6.5 ± 0.8 | 2.4 ± 0.3 | 1.2 ± 0.1 | 1.9 ± 0.2 | 0.4 ± 0.1 | 7.5 ± 1.3 | nd | nd | nd |
Carboplatin | 0.9 ± 0.2 | 1.8 ± 0.2 | 0.5 ± 0.1 | 4.1 ± 0.5 | 2.9 ± 0.4 | 0.9 ± 0.2 | 3.0 ± 1.2 | 0.9 ± 0.2 | nd | nd | nd |
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McGhie, B.S.; Sakoff, J.; Gilbert, J.; Gordon, C.P.; Aldrich-Wright, J.R. Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents. Int. J. Mol. Sci. 2023, 24, 17150. https://doi.org/10.3390/ijms242417150
McGhie BS, Sakoff J, Gilbert J, Gordon CP, Aldrich-Wright JR. Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents. International Journal of Molecular Sciences. 2023; 24(24):17150. https://doi.org/10.3390/ijms242417150
Chicago/Turabian StyleMcGhie, Brondwyn S., Jennette Sakoff, Jayne Gilbert, Christopher P. Gordon, and Janice R. Aldrich-Wright. 2023. "Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents" International Journal of Molecular Sciences 24, no. 24: 17150. https://doi.org/10.3390/ijms242417150