Halogenated PtIV Complexes from N‐Halosuccinimide Oxidation of PtII Antitumor Drugs: Synthesis, Mechanistic Investigation, and Cytotoxicity. Issue 12 (20th December 2016)

• Record Type: Journal Article
• Authors: Xu, Zoufeng; Li, Cai; Tong, Zixuan; Ma, Lili; Tse, Man‐Kit; Zhu, Guangyu
• Other Names: Alessio Enzo guestEditor.; Guo Zijian guestEditor.
• Is Part Of: European journal of inorganic chemistry. Issue 12(2017)
• Page Start: 1706
• Page End: 1712
• Publication Date: 2016-12-20
• Subjects: Platinum -- N‐Halosuccinimide -- Halogenation -- Cisplatin -- Cytotoxicity -- Cancer; Chemistry, Inorganic -- Periodicals; Organometallic chemistry -- Periodicals; Bioinorganic chemistry -- Periodicals; Solid state chemistry -- Periodicals; 546
• DOI: 10.1002/ejic.201601130
• Languages: English
• ISSNs: 1434-1948

Abstract

Abstract : Compared with square‐planar Pt II drugs, Pt IV ‐based anticancer prodrugs are relatively inert under physiological conditions and can be activated after entering cells. The two axial ligands in Pt IV complexes provide an opportunity to further functionalize these prodrugs. In recent years, much effort has been devoted to developing new Pt IV ‐based anticancer prodrugs with higher cytotoxicity but fewer side effects. New synthetic methods, however, are intensely desired for structurally diversified and biologically distinct Pt IV complexes. Herein, we utilize N ‐halosuccinimides as oxidants and carry out the oxidation reaction on Pt II drugs including cisplatin, carboplatin, and oxaliplatin to obtain halogenated Pt IV complexes. The related mechanism of the reaction of N ‐bromosuccinimide (NBS) with cisplatin in ethanol is thoroughly investigated. N ‐chlorosuccinimide is also utilized to obtain the respective dichlorinated Pt IV complexes. When N ‐iodosuccinimide reacts with Pt II drugs, new Pt IV compounds containing iodide and succinimide ligands in the axial position are formed. Cytotoxicity test shows that some of the complexes are active against cisplatin‐resistant human ovarian cancer cells. Our study provides a detailed understanding of the reaction mechanism between NBS and cisplatin and offers a more convenient strategy to obtain dichlorinated and new iodinated Pt IV anticancer prodrugs. Abstract : Halogenated Pt IV anticancer prodrugs are obtained by oxidation of Pt II drugs with N ‐halosuccinimides. A detailed mechanism of the reaction of N ‐bromosuccinimide with cisplatin in ethanol is revealed.