Abstract
The dibromido analogue of cisplatin, cis-PtBr2(NH3)2 (cisPtBr2 hereafter), has been prepared and characterised. Its solution behaviour in standard phosphate buffer, at pH 7.4, was investigated spectrophotometrically and found to reproduce quite closely that of cisplatin; indeed, progressive sequential release of the two halide ligands typically occurs as in the case of cisplatin, with a roughly similar kinetics. Afterward, patterns of reactivity toward model proteins and standard ctDNA were explored and the nature of the resulting interactions elucidated. The antiproliferative properties were then evaluated in four representative cancer cell lines, namely A549 (human lung cancer), HCT116 (human colon cancer), IGROV-1 (human ovarian cancer) and FLG 29.1 (human acute myeloid leukaemia). Cytotoxic properties in line with those of cisplatin were highlighted. From these studies an overall chemical and biological profile emerges for cisPtBr2 closely matching that of cisplatin; the few slight, but meaningful differences that were underscored might be advantageously exploited for clinical application.
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Acknowledgments
We gratefully acknowledge Beneficentia Stiftung, Ente Cassa Risparmio Firenze (ECR), COST Action CM1105 and Università di Pisa (PRA2015-0055) for financial support, CISM (University of Florence) for recording ESI–MS spectra, and Dr. Tarita Biver for a sample of fragmented ctDNA. T.M. thanks AIRC-FIRC (Fondazione Italiana per la Ricerca sul Cancro, 3-years Fellowship for Italy Project Code: 18044). CIRCMSB is also acknowledged.
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Marzo, T., Bartoli, G., Gabbiani, C. et al. Cisplatin and its dibromido analogue: a comparison of chemical and biological profiles. Biometals 29, 535–542 (2016). https://doi.org/10.1007/s10534-016-9934-4
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DOI: https://doi.org/10.1007/s10534-016-9934-4