Shiina Isamu, Sano Yoshiyuki, Nakata Kenya, Kikuchi Takaaki, Sasaki Akane, Ikekita Masahiko, Nagahara Yukitoshi, Hasome Yoshimune, Yamori Takao, Yamazaki Kanami
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Biochem Pharmacol. 2008 Mar 1;75(5):1014-26. doi: 10.1016/j.bcp.2007.11.005. Epub 2007 Nov 22.
Four pseudo-symmetrical tamoxifen derivatives, RID-B (13), RID-C (14), RID-D (15), and bis(dimethylaminophenetole) (16), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of these pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 13 and 16 strongly inhibit the viability of the HL-60 human acute promyelocytic leukemia cell line, whereas 14 possesses a medium activity against the same cell line and 15 has no effect on the cell viability. The global anti-tumor activity of 13-16 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR 39), and it was shown that RID-B (13) strongly inhibited the growth of several cancer cell lines at concentrations of less than 1 microM (at 0.38 microM for SF-539 [central nervous system], at 0.58 microM for HT-29 [colon], at 0.20 microM for DMS114 [lung], at 0.21 microM for LOX-IMVI [melanoma], and at 0.23 microM for MKN74 [stomach]).
通过新型三组分偶联反应合成了四种伪对称他莫昔芬衍生物，即RID - B（13）、RID - C（14）、RID - D（15）和双（二甲基氨基苯乙醚）（16），并研究了这些伪对称他莫昔芬衍生物的构效关系。发现13和16强烈抑制HL - 60人急性早幼粒细胞白血病细胞系的活力，而14对同一细胞系具有中等活性，15对细胞活力无影响。使用一组39种人类癌细胞系（JFCR 39）评估了13 - 16对多种人类癌细胞的整体抗肿瘤活性，结果表明，RID - B（13）在浓度低于1微摩尔时强烈抑制几种癌细胞系的生长（对于SF - 539 [中枢神经系统]为0.38微摩尔，对于HT - 29 [结肠]为0.58微摩尔，对于DMS114 [肺]为0.20微摩尔，对于LOX - IMVI [黑色素瘤]为0.21微摩尔，对于MKN74 [胃]为0.23微摩尔）。
