期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 72, 期 -, 页码 127-136出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2013.11.014
关键词
Dinuclear platinum complex; Polyphosphoester conjugate; DOSY NMR; Cytotoxicity; Proapoptotic activity; Renal epithelial cells; Nephrotoxicity
资金
- NSF of Bulgaria [DO 02-198/2008, DRNF 02-13/2009]
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. H-1 and P-31{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. (C) 2013 Elsevier Masson SAS. All rights reserved.
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