Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P.Bucci, 87036 Rende (CS), Italy.
Phys Chem Chem Phys. 2023 Jun 15;25(23):15586-15599. doi: 10.1039/d3cp01150j.
Octahedral Pt complexes are considered highly promising candidates for overcoming some shortcomings of clinically approved Pt drugs. Pt 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 Pt 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 Pt 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 Pt complexes in biological environments.
八面体 Pt 配合物被认为是克服临床批准的 Pt 药物一些缺点的极具前景的候选物。Pt 化合物由于其惰性，似乎能够抵抗过早的水合作用和与必需的血浆蛋白的不期望的结合，并显示出对口服和减少副作用的显著潜力。此外，通过选择合适的轴向配体，可以精细调整它们的药理学性质。通过生物还原剂在细胞内还原为相应的活性细胞毒性 Pt 物种，伴随着轴向配体的丢失，被认为是其机制的一个重要步骤，并且已经进行了广泛的研究。然而，对于 Pt 前药如何被激活的机制的详细理解，这对于它们的合理设计是非常有益的，但仍有许多矛盾的结果不断被收集。希望为该领域的知识进步做出贡献，本观点重点介绍了通过计算研究获得的见解，目的是为许多关于生物环境中 Pt 配合物还原的仍未解决的问题找到答案。
