Polyphosphoester conjugates of dinuclear platinum complex: Synthesis and evaluation of cytotoxic and the proapoptotic activity

• Polyphosphoester conjugates of a spermidine bridged dinuclear Pt complex were synthesized.
• Drug conjugation was proved using 1Н and 31P{H} DOSY NMR spectral data.
• The conjugates exerted prominent cytotoxicity against human tumor cell lines.
• The dinuclear agents retained activity in a cisplatin-resistant cell line.
• The tested agents evoked cisplatin-dissimilar cell cycle modulation in KG-1 cells.

Macromolecular conjugates of a dinuclear platinum complex with a spermidine bridge were synthesized using poly(oxyethylene H-phosphonate)s as precursor polymer. The complex species were attached to the polymer chain via a phosphoramide bond resulting from the reaction between the H-phosphonate groups and the middle amino group of the spermidine moiety. 1H and 31P{H} DOSY NMR spectral data were used to prove the conjugation reaction and to characterize the new species. The conjugates exhibited profound cytotoxicity in a panel of five chemosensitive human tumor cell lines and one cisplatin-resistant model (HL-60/CDDP), and were found to induce apoptotic cell death. A flow cytometric analysis encountered a cisplatin-dissimilar modulation of the cell cycle progression in KG-1 leukemic cells, following exposure to the dinuclear agents. Moreover, the novel compounds displayed less pronounced inhibitory activity against cultured murine renal epithelial cells, as compared to cisplatin.

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