Synthesis, In Vitro, and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes
Abstract
:1. Introduction
2. Results
2.1. Synthesis
2.2. Inhibitory Activity against PTP1B Phosphatase
- IC50–The obtained half maximal inhibitory concentration for each complexes;
- [S]–substrate concentration (1 mM);
- [Km] = The calculated Michaelis constant (0.7 mM).
2.3. In Silico Studies
2.4. Cytotoxicity against Breast Cancer Cell Lines and Human Keratinocyte Cell Line
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Synthesis
4.3. Recombinant PTP1B Assay
4.4. Cell Lines and Culture
4.5. Cell Viability Assay
4.6. Molecular Modeling
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compounds | IC50 ± SD [nM] | Ki ± SD [nM] |
---|---|---|
1 | 627.5 ± 39.1 | 256.3 ± 15.3 |
2 | 426.3 ± 37.1 | 173.4 ± 17.2 |
3 | 542.8 ± 48.4 | 221.4 ± 19.1 |
4 | 185.4 ± 9.8 | 74.2 ± 4.1 |
5 | 167.2 ± 8.0 | 66.7 ± 3.3 |
Sodium orthovanadate | 204.1 ± 25.15 | 96.8 ± 15.6 |
Open | ||||||||||||
1ONZ | 3EAX | |||||||||||
GS | ΔG[kcal/mol] * | Ki[µM] * | RMSD | GS | ΔG[kcal/mol] * | Ki[µM] * | RMSD | |||||
1 | 40.80 | −5.03 | 147.91 | 0.1 | 38.86 | −5.81 | 48.98 | 0.16 | ||||
2 | 51.52 | −7.65 | 1.23 | 0.12 | 48.42 | −7.08 | 4.57 | 5.19 | ||||
3 | 48.04 | −6.68 | 7.94 | 0.62 | 46.65 | −6.57 | 9.55 | 5.48 | ||||
4 | 60.94 | −8.36 | 0.28 | 0.09 | 45.56 | −7.74 | 1.17 | 6.93 | ||||
Closed | ||||||||||||
1Q6J | 2FJN | 5KAD | ||||||||||
GS | ΔG[kcal/mol] * | Ki[µM] * | RMSD | GS | ΔG[kcal/mol] * | Ki[µM] * | RMSD | GS | ΔG[kcal/mol] * | Ki[µM] * | RMSD | |
1 | 34.84 | −4.66 | 263.03 | 0.21 | 33.94 | −5.08 | 173.78 | 13.29 | 32.60 | −5.77 | 54.95 | 9.35 |
2 | 18.17 | −5.17 | 151.36 | 16.64 | 30.26 | −5.95 | 18.62 | 13.08 | 37.61 | −6.49 | 8.51 | 4.24 |
3 | 24.38 | −5.42 | 56.23 | 14.98 | 32.05 | −5.55 | 60.26 | 17.17 | 32.11 | −5.49 | 53.70 | 6.98 |
4 | 37.55 | −7.28 | 1.95 | 5.01 | 41.39 | −6.95 | 4.37 | 7.66 | 43.66 | −7.08 | 2.57 | 6.3 |
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Kostrzewa, T.; Jończyk, J.; Drzeżdżon, J.; Jacewicz, D.; Górska-Ponikowska, M.; Kołaczkowski, M.; Kuban-Jankowska, A. Synthesis, In Vitro, and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes. Int. J. Mol. Sci. 2022, 23, 7034. https://doi.org/10.3390/ijms23137034
Kostrzewa T, Jończyk J, Drzeżdżon J, Jacewicz D, Górska-Ponikowska M, Kołaczkowski M, Kuban-Jankowska A. Synthesis, In Vitro, and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes. International Journal of Molecular Sciences. 2022; 23(13):7034. https://doi.org/10.3390/ijms23137034
Chicago/Turabian StyleKostrzewa, Tomasz, Jakub Jończyk, Joanna Drzeżdżon, Dagmara Jacewicz, Magdalena Górska-Ponikowska, Marcin Kołaczkowski, and Alicja Kuban-Jankowska. 2022. "Synthesis, In Vitro, and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes" International Journal of Molecular Sciences 23, no. 13: 7034. https://doi.org/10.3390/ijms23137034