Dzhemileva Lilya U, Makarov Alexey A, Andreev Evgeny N, Makarova Elina Kh, Yunusbaeva Milyausha M, D'yakonov Vladimir A, Dzhemilev Usein M
Institute of Petrochemistry and Catalysis of Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation.
ACS Omega. 2020 Jan 23;5(4):1974-1981. doi: 10.1021/acsomega.9b03826. eCollection 2020 Feb 4.
An original method has been developed for the synthesis of 1,3-dyine derivatives of natural lembehyne B in high yields (50-67%) and with high selectivity (>98%). The key stage of the synthesis is new Ti-catalyzed cross-cyclomagnesiation of oxygenated and aliphatic 1,2-dienes induced by Grignard reagents. For studying the effect of the structure on the antitumor and neuritogenic activities, a series of lembehyne B analogues with different distances between the terminal hydroxy group and the 1,3-diyne moiety was prepared and tested for neuritogenic activity on mouse neuroblastoma Neuro 2A cells and for cytotoxicity, induction of apoptosis, and effects on the cell cycle using Jurkat, U937, K562, HeLa, and Hek293 tumor cell lines.
已开发出一种原始方法，可高产率（50 - 67%）且高选择性（>98%）地合成天然lembehyne B的1,3 - 二炔衍生物。合成的关键步骤是由格氏试剂引发的新型钛催化的含氧和脂肪族1,2 - 二烯的交叉环镁化反应。为了研究结构对抗肿瘤和神经突生成活性的影响，制备了一系列在末端羟基与1,3 - 二炔部分之间具有不同距离的lembehyne B类似物，并在小鼠神经母细胞瘤Neuro 2A细胞上测试其神经突生成活性，以及使用Jurkat、U937、K562、HeLa和Hek293肿瘤细胞系测试其细胞毒性、诱导凋亡以及对细胞周期的影响。
