In the present study, we investigated antiproliferative activity of seven newly synthesized chalcone derivatives. Among tested compounds, (2 E)-3-(acridin-9-yl)-1-(2,6-dimethoxyphenyl)prop-2-en-1-one (1C) was the most potent with IC₅₀ = 4.1 μmol/L in human colorectal HCT116 cells and was selected for further studies. Inhibition of cell proliferation was associated with cell cycle arrest in G2/M phase and dysregulation of α, α1 and β5 tubulins. Moreover, 1C caused disruption of the mitochondrial membrane potential and increased number of cells with sub G0/G1 DNA content which is considered as marker of apoptosis. Apoptosis was confirmed by annexin V/PI and AO/PI staining. Furthermore, we found increased concentration of cytochrome c, Smac/Diablo and increased caspase-3 and caspase-9 activity, cleavage of PARP as well as activation of DNA repair mechanisms in 1C-treated HCT116 cancer cells. Moreover this chalcone derivative up-regulated proapoptotic Bax expression and down-regulated antiapoptotic Bcl-2 and Bcl-xL expression. Additionally, 1C treatment led to modulation of MAPKs and Akt signalling pathways.

In conclusion, our data showed ability of 1C to suppress cancel cell growth and provide the rationale for further in vivo study.

在本研究中，我们调查了七个新合成的查尔酮衍生物的抗增殖活性。在测试的化合物中，（2 E）-3-（ac啶-9-基）-1-（2,6-二甲氧基苯基）丙-2-烯-1-一（1C）最有效，IC ₅₀  = 4.1μmol / L在人结肠直肠HCT116细胞中，并被选择作进一步研究。细胞增殖的抑制与在G2 / M期的细胞周期停滞以及α，α1和β5微管蛋白的失调有关。此外，1 C导致线粒体膜电位的破坏和具有亚G0 / G1 DNA含量的细胞数量增加，这被认为是细胞凋亡的标志。膜联蛋白V / PI和AO / PI染色证实了细胞凋亡。此外，我们发现细胞色素c的浓度增加，Smac / Diablo和caspase-3和caspase-9活性增加，PARP的裂解以及1C处理的HCT116癌细胞中DNA修复机制的激活。此外，该查尔酮衍生物上调凋亡前的Bax表达，下调抗凋亡的Bcl-2和Bcl-xL表达。另外，1C处理导致MAPK和Akt信号通路的调节。

总之，我们的数据显示了1C抑制抵消细胞生长的能力，并为进一步的体内研究提供了依据。