Schobert Rainer, Bernhardt Günther, Biersack Bernhard, Bollwein Susanne, Fallahi Magid, Grotemeier Antje, Hammond Geoffrey L
Organisch-chemisches Laboratorium der Universität, 95447 Bayreuth, Germany.
ChemMedChem. 2007 Mar;2(3):333-42. doi: 10.1002/cmdc.200600173.
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.
将6-氨甲基烟酸与各种甾体醇形成的酯用K₂PtCl₄处理，得到N,N-螯合的二氯铂（II）配合物共轭物4。通过电泳迁移率测量监测它们与质粒DNA的相互作用。通过竞争性置换放射分析评估它们对性激素结合球蛋白（SHBG）和核雌激素受体ERα的亲和力。在体外研究了4对乳腺肿瘤细胞MCF-7 ER(+)/ER(-)和MDA-MB-231的抑制作用。与3-O-连接的雌激素4 a、b或17-O-连接的雄激素4 g形成的共轭物与SHBG强烈结合。具有3-O-连接雌二醇的共轭配合物4 b也与雌激素受体强烈且激动性地结合。它还引起MCF-7（ER(+)）细胞明显的生长迟缓，推测其机制与顺铂不同。
