Issue 23, 2023

The current status in computational exploration of Pt(iv) prodrug activation by reduction

Abstract

Octahedral PtIV complexes are considered highly promising candidates for overcoming some shortcomings of clinically approved PtII drugs. PtIV compounds, owing to their inertia, appear to be capable of resisting premature aquation and undesired binding to essential plasma proteins and have shown remarkable potential for both oral administration and for reducing side effects. Additionally, their pharmacological properties can be finely tuned by choosing appropriate axial ligands. The reduction inside the cell by biological reducing agents to the correponding active cytotoxic PtII species, accompanied by the loss of the axial ligands, is considered an essential step of their mechanism and has been extensively studied. However, a detailed understanding of the mechanism by which PtIV prodrugs are activated, which should be highly beneficial for their proper design, is lacking, and many contradictory results continue to be collected. In the hope of contributing to the advancement of knowledge in this field, this perspective focuses on the insights gained from computational studies carried out with the aim of finding answers to the many still open questions concerning the reduction of PtIV complexes in biological environments.

Graphical abstract: The current status in computational exploration of Pt(iv) prodrug activation by reduction

Article information

Article type
Perspective
Submitted
13 mrt 2023
Accepted
17 mei 2023
First published
18 mei 2023
This article is Open Access
Creative Commons BY-NC license

Phys. Chem. Chem. Phys., 2023,25, 15586-15599

The current status in computational exploration of Pt(IV) prodrug activation by reduction

F. Ponte, S. Scoditti, G. Mazzone and E. Sicilia, Phys. Chem. Chem. Phys., 2023, 25, 15586 DOI: 10.1039/D3CP01150J

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