LSD1小分子抑制剂的合成及抗肿瘤活性研究

发布时间：2018-05-17 22:41

本文选题：LSD + 小分子抑制剂　；参考：《化学试剂》2017年08期

【摘要】：设计并合成了一系列以苯甲酰肼类结构为母核的赖氨酸特异性组蛋白去甲基化酶1(LSD1)小分子抑制剂,并研究其体外抗肿瘤活性。首先,通过体外酶水平单浓度抑制实验进行了初步评价,并随后进一步考察目标化合物对多种LSD1高表达肿瘤细胞株增殖的抑制作用,化合物结构经质谱及核磁共振表征确证。活性评价结果显示,3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)-N'-(7-羟基-2,3-二氢-1H-茚-1-亚基)苯甲酰肼、N'-(1-(5-氯-2-羟基苯基)亚乙基)-3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)苯甲酰肼和N'-(4-氯-7-羟基-2,3-二氢-1H-茚-1-亚基)-3-((4-吗啉代哌啶-1-基)磺酰基)苯甲酰肼可显著抑制肿瘤细胞的增殖,并有4个目标化合物对体外多种LSD1高表达的肿瘤细胞株增殖有抑制作用,其中3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)-N'-(7-羟基-2,3-二氢-1H-茚-1-亚基)苯甲酰肼对BGC823、HCT116、A2780s的半数抑制浓度分别为0.32、0.54、0.90μmol/L。
[Abstract]:A series of Lysine-specific histone demethylase (LSD1) small molecular inhibitors with benzoylhydrazide structure as maternal nucleus were designed and synthesized, and their antitumor activities in vitro were studied. The inhibition effect of the target compounds on the proliferation of various LSD1 overexpression tumor cell lines was investigated. The structure of the compounds was confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). The results of the activity evaluation showed that 3- (3) 3R ~ (- 5) S ~ (- 3) S ~ (- 3) -dimethylmorpholine) sulfonyl) (benzoyl hydrazine) and Na-4-chloro-7- (-hydroxy-2-hydroxyphenyl) benzoylhydrazide) (Na-4-chloro-7-hydroxy-2-hydroxyhydrazide) ethylene-3-trichloro-5-chloro-2-hydroxyphenyl) benzoyl hydrazide and Na-4chloro-7- hydroxy-23- dioxy) sulfonyl group). The proliferation of tumor cells was significantly inhibited by hydro-1H-inden-1-subunit, 4-morpholine, piperidine-1-yl) sulfonyl) benzoyl hydrazine. Four target compounds could inhibit the proliferation of tumor cell lines with high expression of LSD1 in vitro, and the half inhibitory concentration of BGC823HCT116A27s was 0.32o 0.540.90 渭 mol / L, respectively. The inhibitory concentration of BGC823HCT116A27s was 0.32o 0.540.90 渭 mol / L for BGC823HCT116A27s, and the inhibitory concentration of BGC823HCT116A27s was 0.32O0.540.90 渭 mol / L for BGC823HCT116A27s.
【作者单位】：江苏食品药品职业技术学院药学院;
【分类号】：R914;R96

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