title: (Arene)Cl₂Ru(II) complexes with N-coordinated estrogen and androgen isonicotinates: interaction with sex hormone binding globulin and anticancer activity.
abstract: (Arene)dichloridoruthenium(II) complexes with N-coordinated isonicotinates of androgens (6) and estrogens (9) were prepared and tested for affinity to the estrogen receptor (ERα) and sex hormone binding globulin (SHBG), as well as for cytotoxicity in cancer cells. None of the new complexes bound noticeably to the ER and most of them also bound less strongly to SHBG than the corresponding unmetallated steroids 7. In MTT assays the Ru(p-cymene) complexes 9 of 2-substituted estrones were equally or even more cytotoxic than the metal-free steroids against hormone-dependent (MCF-7 breast and KB-V1 cervix carcinomas) and hormone-independent (518A2 melanoma) cells. The addition of external SHBG to MTT assays lowered the cytotoxicities of the complexes 9 and distinctly more so those of some steroids 7, probably by the way of sequestration and reduction of the cellular uptake. In the absence of SHBG the estrogen complexes 9 were internalized by 518A2 melanoma cells and ruthenated their DNA as quantified by ICP-OES. They also ruthenated salmon sperm DNA but did not change the topology of plasmid DNA in EMSA experiments. In addition, the Ru(p-cymene) complex of 2-ethoxyestrone (9c) was shown to reduce the motility of 518A2 melanoma cells in a wound-healing assay.
authors.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, D-95440 Bayreuth, Germany. Rainer.Schobert@uni-bayreuth.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seibt
authors.forename: Katharina
authors.initials: K
authors.lastname: Effenberger-Neidnicht
authors.forename: Caroline
authors.initials: C
authors.lastname: Underhill
authors.forename: Bernhard
authors.initials: B
authors.lastname: Biersack
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Hammond
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D045166:Estradiol Congeners / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007539:Isonicotinic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism; D012428:Ruthenium; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D045165:Testosterone Congeners / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D045166:Estradiol Congeners; D007539:Isonicotinic Acids; D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin; D045165:Testosterone Congeners; D012428:Ruthenium