Justin J Wilson1, Stephen J Lippard. 1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Abstract
Five cationic platinum(II) complexes of general formula, [Pt(NH(3))(2)(β-diketonate)]X are reported, where X is a noncoordinating anion and β-diketonate = acetylacetonate (acac), 1,1,1,-trifluoroacetylacetonate (tfac), benzoylacetonate (bzac), 4,4,4-trifluorobenzoylacetonate (tfbz), or dibenzoylmethide (dbm), corresponding, respectively, to complexes 1-5. The log P values and the stabilities of 1-5 in aqueous solution were evaluated. The phenyl ring substituents of 3-5 increase the lipophilicity of the resulting complexes, whereas the trifluoromethyl groups of 2 and 4 decrease the stability of the complexes in aqueous solution. The uptake of 1-5 in HeLa cells increases as the lipophilicity of the investigated complex increases. Cancer cell cytotoxicity studies indicate that 1 and 3 are the least active complexes whereas 2, 4, and 5 are comparable in activity to cisplatin.
Five cationic platinum(II) complexes of general formula, [n class="Chemical">Pt(NH(3))(2)(β-diketonate)]X are reported, where X is a noncoordinating anion and β-diketonate = acetylacetonate (acac), 1,1,1,-trifluoroacetylacetonate (tfac), benzoylacetonate (bzac), 4,4,4-trifluorobenzoylacetonate (tfbz), or dibenzoylmethide (dbm), corresponding, respectively, to complexes 1-5. The log P values and the stabilities of 1-5 in aqueous solution were evaluated. The phenyl ring substituents of 3-5 increase the lipophilicity of the resulting complexes, whereas the trifluoromethyl groups of 2 and 4 decrease the stability of the complexes in aqueous solution. The uptake of 1-5 in HeLa cells increases as the lipophilicity of the investigated complex increases. Cancer cell cytotoxicity studies indicate that 1 and 3 are the least active complexes whereas 2, 4, and 5 are comparable in activity to cisplatin.
Authors: Erin S F Ma; W Douglas Bates; Armistead Edmunds; Lloyd R Kelland; Tito Fojo; Nicholas Farrell Journal: J Med Chem Date: 2005-09-08 Impact factor: 7.446
Authors: Shuzhong Zhang; Katherine S Lovejoy; James E Shima; Leah L Lagpacan; Yan Shu; Anna Lapuk; Ying Chen; Takafumi Komori; Joe W Gray; Xin Chen; Stephen J Lippard; Kathleen M Giacomini Journal: Cancer Res Date: 2006-09-01 Impact factor: 12.701
Authors: A Muscella; N Calabriso; F P Fanizzi; S A De Pascali; L Urso; A Ciccarese; D Migoni; S Marsigliante Journal: Br J Pharmacol Date: 2007-11-19 Impact factor: 8.739
Authors: Simon P Wisnovsky; Justin J Wilson; Robert J Radford; Mark P Pereira; Maria R Chan; Rebecca R Laposa; Stephen J Lippard; Shana O Kelley Journal: Chem Biol Date: 2013-10-31
Authors: A Muscella; C Vetrugno; D Migoni; F Biagioni; F P Fanizzi; F Fornai; S A De Pascali; S Marsigliante Journal: Cell Death Dis Date: 2014-01-23 Impact factor: 8.469