Improvement of Kiteplatin Efficacy by a Benzoato Pt(IV) Prodrug Suitable for Oral Administration
Abstract
:1. Introduction
2. Results and Discussion
2.1. Stability at Acidic pH
2.2. Electrochemical Characterization
2.3. Characterization of the Surface Reduction
2.4. Reduction of Complex 1 by Bioreductants
2.4.1. Reduction of cis,trans,cis-[PtCl2(OBz)2(cis-1,4-DACH)] by Ascorbic Acid/Sodium Ascorbate
2.4.2. Reduction of cis,trans,cis-[PtCl2(OBz)2(cis-1,4-DACH)] by Glutathione
2.5. In Vivo Antitumor Activity
2.6. Neurotoxicity Studies
3. Materials and Methods
3.1. Starting Materials and Instrumental Details
3.2. Synthesis of cis,trans,cis-[PtCl2(OBz)2(cis-1,4-DACH)] (1; OBz = Benzoate = OOCC6H5)
3.3. Stability at Acidic pH
3.4. Reduction by Biological Reducing Agents
3.4.1. Ascorbic Acid/Ascorbate
3.4.2. Glutathione
3.5. In Vivo Antitumor Activity
3.5.1. Experiments with Animals
3.5.2. In Vivo Antitumor Activity in Lewis Lung Carcinoma (LLC)
3.6. Neurotoxicity Studies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | Daily Dose (mg/Kg) | Average Tumor Weight (Mean ± S.D., g) | Inhibition of Tumor Growth (%) |
---|---|---|---|
Control a | - | 0.40 ± 0.07 | - |
1 | 5 | 0.11 ± 0.08 | 72.5 |
cisplatin | 1.5 | 0.09 ± 0.02 | 77.5 |
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Barbanente, A.; Gandin, V.; Ceresa, C.; Marzano, C.; Ditaranto, N.; Hoeschele, J.D.; Natile, G.; Arnesano, F.; Pacifico, C.; Intini, F.P.; et al. Improvement of Kiteplatin Efficacy by a Benzoato Pt(IV) Prodrug Suitable for Oral Administration. Int. J. Mol. Sci. 2022, 23, 7081. https://doi.org/10.3390/ijms23137081
Barbanente A, Gandin V, Ceresa C, Marzano C, Ditaranto N, Hoeschele JD, Natile G, Arnesano F, Pacifico C, Intini FP, et al. Improvement of Kiteplatin Efficacy by a Benzoato Pt(IV) Prodrug Suitable for Oral Administration. International Journal of Molecular Sciences. 2022; 23(13):7081. https://doi.org/10.3390/ijms23137081
Chicago/Turabian StyleBarbanente, Alessandra, Valentina Gandin, Cecilia Ceresa, Cristina Marzano, Nicoletta Ditaranto, James D. Hoeschele, Giovanni Natile, Fabio Arnesano, Concetta Pacifico, Francesco P. Intini, and et al. 2022. "Improvement of Kiteplatin Efficacy by a Benzoato Pt(IV) Prodrug Suitable for Oral Administration" International Journal of Molecular Sciences 23, no. 13: 7081. https://doi.org/10.3390/ijms23137081