title: Steroid conjugates of dichloro(6-aminomethylnicotinate)platinum(II): effects on DNA, sex hormone binding globulin, the estrogen receptor, and various breast cancer cell lines.
abstract: Esters of 6-aminomethylnicotinic acid with various steroidal alcohols were treated with K(2)PtCl(4) to give the N,N-chelated dichloroplatinum(II) complex conjugates 4. Their interaction with plasmid DNA was monitored by electrophoretic mobility measurements. Their affinities towards sex hormone binding globulin (SHBG) and towards the nuclear estrogen receptor ER(alpha) were assessed by competitive displacement radioassays. The inhibitory effect of 4 on breast tumour cells MCF-7 ER(+)/ER(-) and MDA-MB-231 was investigated in vitro. Conjugates with 3-O-linked estrogens 4 a,b or 17-O-linked androgens 4 g bound strongly to SHBG. The conjugate complex 4 b, featuring a 3-O-linked estradiol, also bound strongly and agonistically to the estrogen receptor. It also elicited distinct growth retardation of MCF-7 (ER(+)) cells, presumably by a mechanism different from that of cisplatin.
authors.affiliation: Organisch-chemisches Laboratorium der Universität, 95447 Bayreuth, Germany. Rainer.Schobert@uni-bayreuth.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
authors.forename: Günther
authors.initials: G
authors.lastname: Bernhardt
authors.forename: Bernhard
authors.initials: B
authors.lastname: Biersack
authors.forename: Susanne
authors.initials: S
authors.lastname: Bollwein
authors.forename: Magid
authors.initials: M
authors.lastname: Fallahi
authors.forename: Antje
authors.initials: A
authors.lastname: Grotemeier
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Hammond
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013256:Steroids / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin; D013256:Steroids; C530248:dichloro(6-aminomethylnicotinate)platinum(II); D004958:Estradiol; D004247:DNA; D002945:Cisplatin