title: Cell-selective, apoptosis-inducing rhodium(III) crown thiaether complexes.
abstract: Half-sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7-trithiacyclononane [9]aneS(3) represent a promising class of apoptosis-inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the human cancer cell lines MCF-7 and HT-29 and immortalized HEK-293 cells indicate that the dicationic kappa(2)N(imino) complexes [([9]aneS(3))RhCl(pp)](2+) are much more active than monocationic complexes [([9]aneS(3))RhCl(2)(L)](+) (L=imidazole, CH(3)CN). Whereas the kappa(2)N(amino) complex [([9]aneS(3))RhCl(piperazine)](2+) is inactive, replacing piperazine with the structurally analogous kappa(2)S (thiaether) ligand 1,4-dithiane restores cytotoxicity as evidenced by IC(50) values in the range 8.1-11.6 microM. Spectroscopic (CD, UV/Vis, NOESY) and viscosity measurements indicate that the active dppz complex 8 (IC(50) values: 4.7-8.9 microM) exhibits strong intercalative binding towards DNA whereas the even more potent bipyrimidine complex 9 (IC(50) values: 0.6-1.9 microM) causes no alteration of the duplex B conformation. Weaker intercalative binding is observed for the dpq complex 7. A comparative annexin V-propidium iodide binding assay with lymphoma (BJAB) cells and healthy leukocytes demonstrates that the cytotoxic activity of complex 8 and particularly complex 9 is highly selective towards the malignant cells.
authors.affiliation: Lehrstuhl für Analytische Chemie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Bieda
authors.forename: Mara
authors.initials: M
authors.lastname: Dobroschke
authors.forename: Annika
authors.initials: A
authors.lastname: Triller
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Marc
authors.initials: M
authors.lastname: Spehr
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
authors.forename: Aram
authors.initials: A
authors.lastname: Prokop
authors.forename: William S
authors.initials: WS
authors.lastname: Sheldrick
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D047248:Crown Compounds / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D012238:Rhodium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D056831:Coordination Complexes; D047248:Crown Compounds; D012238:Rhodium