title: Biological activity of neutral and cationic iridium(III) complexes with κP and κP,κS coordinated Ph₂PCH₂S(O)xPh (x = 0-2) ligands.
abstract: Neutral iridium(III) complexes of the type [Ir(η(5)-C₅Me₅)Cl₂{Ph₂PCH₂S(O)xPh-κP}] (1-3) with diphenylphosphino-functionalized methyl phenyl sulfides, sulfoxides, and sulfones Ph₂PCH₂S(O)xPh (x = 0, L1; 1, L2; 2, L3) and the cationic complex [Ir(η(5)-C₅Me₅)Cl{Ph₂PCH₂SPh-κP,κS}][PF6] (4) were synthesized and fully characterized analytically and spectroscopically. Furthermore, the structure of 2 was determined by X-ray diffraction analysis. The biological potential of the neutral and cationic iridium(III) complexes was tested in vitro against the cell lines 8505C, A253, MCF-7, SW480 and 518A2. Complex [Ir(η(5)-C₅Me₅)Cl₂{Ph₂PCH₂S(O)Ph-κP}] (2), with ligand L2 κP coordinated containing a pendent sulfinyl group, is the most active one (IC₅₀ values of about 3 μM), thus, with activities comparable to cisplatin. Complex 2 proved to have an even a higher antiproliferative activity than cisplatin against 8505C and SW480 cell lines, used as a model system of highly anaplastic cancers with low sensitivity to conventional chemotherapeutics such as cisplatin. Additional experiments demonstrated that apoptosis and autophagic cell death contribute to the drug's tumoricidal action.
authors.affiliation: Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, D-06120 Halle, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Ludwig
authors.forename: Sanja
authors.initials: S
authors.lastname: Mijatović
authors.forename: Ivan
authors.initials: I
authors.lastname: Ranđelović
authors.forename: Mirna
authors.initials: M
authors.lastname: Bulatović
authors.forename: Djordje
authors.initials: D
authors.lastname: Miljković
authors.forename: Danijela
authors.initials: D
authors.lastname: Maksimović-Ivanić
authors.forename: Marcus
authors.initials: M
authors.lastname: Korb
authors.forename: Heinrich
authors.initials: H
authors.lastname: Lang
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinborn
authors.forename: Goran N
authors.initials: GN
authors.lastname: Kaluđerović
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D008024:Ligands; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D008024:Ligands; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D007495:Iridium; D002945:Cisplatin
keywords: Cytotoxic activity; Iridium(III) complexes; Sulfur-functionalized phosphorus ligands