Multifunctional Pt(iv) prodrug candidates featuring the carboplatin core and deferoxamine.

Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101176026 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9234 (Electronic) Linking ISSN: 14779226 NLM ISO Abbreviation: Dalton Trans Subsets: MEDLINE

Original Publication: Cambridge, UK : Royal Society of Chemistry, c2003-

Antineoplastic Agents/*pharmacology ; Carboplatin/*pharmacology ; Deferoxamine/*pharmacology ; Organoplatinum Compounds/*pharmacology ; Prodrugs/*pharmacology; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Carboplatin/chemistry ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Deferoxamine/chemistry ; Drug Screening Assays, Antitumor ; Humans ; Molecular Structure ; Organoplatinum Compounds/chemical synthesis ; Organoplatinum Compounds/chemistry ; Prodrugs/chemical synthesis ; Prodrugs/chemistry ; Tumor Cells, Cultured

The synergistic combination of the anticancer drug carboplatin and the iron chelator deferoxamine (DFO) served as a foundation for the development of novel multifunctional prodrugs. Hence, five platinum(iv) complexes, featuring the equatorial coordination sphere of carboplatin, and one or two DFO units incorporated at axial positions, were synthesized and characterized using ESI-HRMS, multinuclear ( ¹ H, ¹³ C, ¹⁵ N, ¹⁹⁵ Pt) NMR spectroscopy and elemental analysis. Analytical studies demonstrated that the chelating properties of the DFO moiety were not compromised after coupling to the platinum(iv) core. The cytotoxic activity of the compounds was evaluated in monolayer (2D) and spheroid (3D) cancer cell models, derived from ovarian teratocarcinoma (CH1/PA-1), colon carcinoma (SW480) and non-small cell lung cancer (A549). The platinum(iv)-DFO prodrugs demonstrated moderate in vitro cytotoxicity (a consequence of their slow activation kinetics) but with less pronounced differences between intrinsically chemoresistant and chemosensitive cell lines as well as between 2D and 3D models than the clinically used platinum(ii) drug carboplatin.

0 (Antineoplastic Agents)
0 (Organoplatinum Compounds)
0 (Prodrugs)
BG3F62OND5 (Carboplatin)
J06Y7MXW4D (Deferoxamine)

Date Created: 20210525 Date Completed: 20211129 Latest Revision: 20211129

20221213

10.1039/d1dt00214g

34031671