Ambros R, Schneider M R, von Angerer S
Institut für Pharmazie, Universität Regensburg, Federal Republic of Germany.
J Med Chem. 1990 Jan;33(1):153-60. doi: 10.1021/jm00163a026.
A number of acetoxy-substituted 5,6-dihydroindolo[2,1-a]isoquinolines were synthesized and tested for binding affinity for steroid hormone receptors. All of the derivatives bind to the estrogen receptor with RBA values ranging from 1.5 to 17 (17 beta-estradiol = 100). Some of them show binding affinities for the androgen receptor as well. In the mouse uterine weight test, the tetracycles proved to be weak estrogens with partial antagonistic activity. All of the compounds were tested in vitro for cytostatic activity with hormone-independent MDA-MB 231 and hormone-dependent MCF-7 breast cancer cells. A cytostatic effect was found in both cell lines. The comparison of results exhibited a stronger inhibitory effect on MCF-7 cells only for compounds with high binding affinity for the estrogen receptor. For those derivatives, it can be assumed that the growth inhibition is partly mediated by the estrogen receptor.
合成了多种乙酰氧基取代的5,6-二氢吲哚并[2,1-a]异喹啉，并测试了它们对类固醇激素受体的结合亲和力。所有衍生物均与雌激素受体结合，相对结合活性（RBA）值范围为1.5至17（17β-雌二醇=100）。其中一些还显示出对雄激素受体的结合亲和力。在小鼠子宫重量试验中，这些四环化合物被证明是具有部分拮抗活性的弱雌激素。所有化合物均在体外针对激素非依赖性MDA-MB 231和激素依赖性MCF-7乳腺癌细胞进行了细胞生长抑制活性测试。在两种细胞系中均发现了细胞生长抑制作用。结果比较表明，仅对雌激素受体具有高结合亲和力的化合物对MCF-7细胞具有更强的抑制作用。对于那些衍生物，可以推测生长抑制部分是由雌激素受体介导的。
