Angélique Kergreis1, Rianne M Lord1,2, Sarah J Pike1,3. 1. School of Chemistry and Biosciences, Faculty of Life Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK. 2. School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. 3. School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Abstract
A series of cyclometallated mono- and di-nuclear platinum(II) complexes and the parent organic ligand, 2,6-diphenylpyridine 1 (HC^N^CH), have been synthesized and characterized. This library of compounds includes [(C^N^C)PtII (L)] (L=dimethylsulfoxide (DMSO) 2 and triphenylphosphine (PPh3 ) 3) and [((C^N^C)PtII )2 (L')] (where L'=N-heterocycles (pyrazine (pyr) 4, 4,4'-bipyridine (4,4'-bipy) 5 or diphosphine (1,4-bis(diphenylphosphino)butane (dppb) 6). Their cytotoxicity was assessed against four cancerous cell lines and one normal cell line, with results highlighting significantly increased antiproliferative activity for the dinuclear complexes (4-6), when compared to the mononucleated species (2 and 3). Complex 6 is the most promising candidate, displaying very high selectivity towards cancerous cells, with selectivity index (SI) values >29.5 (A2780) and >11.2 (A2780cisR), and outperforming cisplatin by >4-fold and >18-fold, respectively.
A series of cyclometallated mono- and di-nuclear n class="Chemical">platinum(II) complexes and the parent organic ligand, 2,6-diphenylpyridine 1 (HC^N^CH), have been synthesized and characterized. This library of compounds includes [(C^N^C)PtII (L)] (L=dimethylsulfoxide (DMSO) 2 and triphenylphosphine (PPh3 ) 3) and [((C^N^C)PtII )2 (L')] (where L'=N-heterocycles (pyrazine (pyr) 4, 4,4'-bipyridine (4,4'-bipy) 5 or diphosphine (1,4-bis(diphenylphosphino)butane (dppb) 6). Their cytotoxicity was assessed against four cancerous cell lines and one normal cell line, with results highlighting significantly increased antiproliferative activity for the dinuclear complexes (4-6), when compared to the mononucleated species (2 and 3). Complex 6 is the most promising candidate, displaying very high selectivity towards cancerous cells, with selectivity index (SI) values >29.5 (A2780) and >11.2 (A2780cisR), and outperforming cisplatin by >4-fold and >18-fold, respectively.
Authors: Miguel Baya; Úrsula Belío; Israel Fernández; Sara Fuertes; Antonio Martín Journal: Angew Chem Int Ed Engl Date: 2016-04-25 Impact factor: 15.336