N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, Moscow 119991, Russia.
N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia.
J Steroid Biochem Mol Biol. 2023 Apr;228:106245. doi: 10.1016/j.jsbmb.2022.106245. Epub 2023 Jan 3.
An elegant approach to unknown secosteroid-quinoline hybrids is disclosed. A series of 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-(iso)quinolylmethylene]hydrazides was prepared and these novel type of secosteroids was screened for antiproliferative activity against estrogen-responsive human breast cancer cell line MCF-7. Most of the synthesized compounds showed a cytotoxic effect superior to that of reference drug cisplatin; the lead compound exhibits the highest activity with the IC value of about 0.8 μM and is 7 times more active than cisplatin. A high selectivity index was observed for the hit 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-quinolylmethylene]hydrazides 2a and 2c. Compounds 2a and 2c evaluated in luciferase reporter assays exhibited high antiestrogenic potency which was superior to that of tamoxifen. These hit compounds were characterized by high activity against MCF-7 cells that retained towards multidrug-resistant NCI/ADR-RES cells.
一种将未知甾体-喹啉杂合体转化为简体中文的优雅方法被揭示。一系列 13,17-去甲甾体-1,3,5(10)-三烯-17-酸[N'-(异)喹啉基亚甲基]腙被制备出来，这些新型甾体化合物被筛选出对雌激素反应性人乳腺癌细胞系 MCF-7 的抗增殖活性。大多数合成的化合物表现出比参考药物顺铂更好的细胞毒性作用；先导化合物表现出最高的活性，IC 值约为 0.8 μM，比顺铂活性高 7 倍。对于命中化合物 13,17-去甲甾体-1,3,5(10)-三烯-17-酸[N'-喹啉基亚甲基]腙 2a 和 2c，观察到高选择性指数。在荧光素酶报告基因测定中评估的化合物 2a 和 2c 表现出的抗雌激素活性优于他莫昔芬。这些命中化合物的特点是对 MCF-7 细胞具有高活性，并且对多药耐药性 NCI/ADR-RES 细胞具有保留性。
