D'yakonov Vladimir A, Tuktarova Regina A, Dzhemileva Lilya U, Ishmukhametova Svetlana R, Yunusbaeva Milyausha M, Dzhemilev Usein M
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, 450075 Ufa, Russian Federation.
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, 450075 Ufa, Russian Federation.
Steroids. 2018 Oct;138:6-13. doi: 10.1016/j.steroids.2018.06.004. Epub 2018 Jun 8.
Hybrid molecules based on a number of steroids (cholesterol, pregnenolone, androsterone) and 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid linked via mono- and diethylene glycol spacers were synthesized for the first time and studied for antitumor activity in vitro. The acid was prepared using catalytic cyclomagnesiation of oxygenated 1,2-dienes with Grignard reagent in the presence of CpTiCl as the key synthetic step. Using flow cytometry, the new molecules were shown for the first time to be efficient apoptosis inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell cultures and to have dose-dependent effect on the S and G2 phases of the cell cycle.
首次合成了基于多种甾体（胆固醇、孕烯醇酮、雄甾酮）和通过单乙二醇和二乙二醇间隔基连接的1,14-十四碳-5Z,9Z-二烯二羧酸的杂化分子，并对其体外抗肿瘤活性进行了研究。该酸的制备以含氧1,2-二烯与格氏试剂在CpTiCl存在下的催化环镁化反应为关键合成步骤。使用流式细胞术首次表明，这些新分子在HeLa、Hek293、U937、Jurkat和K562细胞培养物中是有效的凋亡诱导剂，并且对细胞周期的S期和G2期具有剂量依赖性作用。
