Reevaluating the Mechanistic Insights of α-TOS-Bearing Pt(IV) Anticancer Complexes: A New Perspective from a More In-Depth Knowledge

Pt(IV) prodrugs have been extensively studied over the years with the aim of overcoming the limitations of traditional Pt(II) drugs. In this frame, two cisplatin-based Pt(IV) complexes bearing α-tocopherol succinate (α-TOS, a derivative of vitamin E) in the axial position (namely, [PtCl2(NH3)2(OEt)(α-TOS)] and [PtCl2(NH3)2(α-TOS)2] were reported in recent years and their cytotoxicity was evaluated. In particular, [PtCl2(NH3)2(OEt)(α-TOS)] was reported to be more cytotoxic than [PtCl2(NH3)2(α-TOS)2]. In the present comment paper, reasons for the different cytotoxicity of these complexes are discussed in detail and, more in general, a comprehensive elucidation of the mechanism of action of this class of anticancer Pt(IV) compounds is provided. Hopefully, these findings and the resulting improved knowledge of these drugs will help researchers design new and improved Pt(IV) anticancer drugs.