title: In vitro anticancer activity of cis-diammineplatinum(II) complexes with β-diketonate leaving group ligands.
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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002412:Cations; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D010984:Platinum; D012995:Solubility; D012997:Solvents; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D056831:Coordination Complexes; D007659:Ketones; D008024:Ligands; D012997:Solvents; D014867:Water; D010984:Platinum; D004247:DNA