Design, synthesis of 4,5-diazafluorene derivatives and their anticancer activity via targeting telomeric DNA G-quadruplex
作者:Kang Zhou、Jiachun Liu、Xuqiong Xiong、Mei Cheng、Xiaolin Hu、Suresh Narva、Xiaoyin Zhao、Yanling Wu、Wen Zhang
DOI:10.1016/j.ejmech.2019.06.012
日期:2019.9
iazole moieties were designed, synthesized, preliminarily explored for their antitumor activities and in vitro mechanism. All compounds showed different values of antiproliferative activity against A549, AGS, HepG2 and MCF-7 cell lines through CCK-8. Especially, the compound 14c exhibited the strongest activity and best selectivity against A549 cells with an IC50 1.13 μM and an SI value of 7.01 relative
在我们的工作中,有19种新颖的4,5-二氮杂芴衍生物(11a-d,12a-d,13a-d,14a-c,15c,16a-c),带有1,3-二取代的吡唑/噻吩并恶唑烷酮或噻吩并噻唑烷酮-恶二唑部分设计,合成,初步探讨了它们的抗肿瘤活性和体外机制。所有化合物通过CCK-8对A549,AGS,HepG2和MCF-7细胞系均显示出不同的抗增殖活性值。尤其是,化合物14c对具有IC 50的A549细胞表现出最强的活性和最佳的选择性相对于MRC-5细胞,1.13μM和SI值为7.01,优于顺铂(SI = 1.80)作为阳性对照。在细胞外水平的实验结果表明,化合物14a-c可以与26 nt端粒富G的DNA中形成的G-四链体强烈相互作用,特别是14c表现出相当强的结合亲和力和缔合平衡常数(K A)为7.04(±0.16)×10 7 M -1,并且以1:1的化合物/ G4-DNA比率,对ds-DNA和Mut