title: Dual antitumor and antiangiogenic activity of organoplatinum(II) complexes.
abstract: A library of over 20 cycloplatinated compounds of the type [Pt(dmba-R)LCl] (dmba-R = C,N-dimethylbenzylamine-like ligand; R being MeO, Me, H, Br, F, CF3, and NO2 substituents in the R5 or R4 position of the phenyl ring; L = DMSO and P(C6H4CF3-p)3) has been prepared. All compounds are active in both human ovarian carcinoma A2780 cells and cisplatin-resistant A2780cisR cells, with most of the DMSO platinum complexes exhibiting IC50 values in the submicromolar range in the A2780 cell line. Interestingly, DMSO platinum complexes show low cytotoxicity in the nontumorigenic kidney cell line BGM and therefore high selectivity factors SF. In addition, some of the DMSO platinum complexes effectively inhibit angiogenesis in the human umbilical vein endothelial cell line EA.hy926. These are the first platinum(II) complexes reported to inhibit angiogenesis at a close concentration to their IC50 in A2780 cells, turning them into dual cytotoxic and antiangiogenic compounds.
authors.affiliation: Departamento de Química Inorgánica and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, and Institute for Bio-Health Research of Murcia (IMIB-Arrixaca) , E-30071 Murcia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Zamora
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Pérez
authors.forename: Venancio
authors.initials: V
authors.lastname: Rodríguez
authors.forename: Christoph
authors.initials: C
authors.lastname: Janiak
authors.forename: Gorakh S
authors.initials: GS
authors.lastname: Yellol
authors.forename: José
authors.initials: J
authors.lastname: Ruiz
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds