设计、合成和评估了一系列基于吡啶的1,2,4-三唑连接的吲哚类共轭物，用于抗增殖活性测试对六种人类癌细胞系进行了检测。所有合成的共轭物（14a-q）均显示出对HT-29细胞系的有效性。特别是14a、14n和14q共轭物表现出有希望的细胞毒性，其IC50值分别为1μM、2.4μM和3.6μM，而标准的5-氟尿嘧啶（IC50 =5.31μM）则比较。这些化合物引起了细胞周期在G0/G1期的阻滞，干扰了线粒体膜电位，增强了总ROS产生。Western blot和免疫荧光实验说明这些化合物抑制与β-连环蛋白和PI3K通路有关的标记物的表达。分子动力学模拟显示，化合物14a在PI3K和坦克酪蛋白蛋白中具有主要的疏水作用和少量的氢键作用。 ©2023美国化学会。

A library of pyridine-based 1,2,4-triazolo-tethered indole conjugates were designed, synthesized, and evaluated for anti-proliferative activity against a panel of six human cancer cell lines. All the synthesized conjugates (14a-q) were found to be effective against the HT-29 cell line. Particularly conjugates 14a, 14n, and 14q exhibited promising cytotoxicity, with IC50 values of 1 μM, 2.4 μM, and 3.6 μM, respectively, compared to the standard 5-fluorouracil (IC50 = 5.31 μM). Cell cycle arrest at the G0/G1 phase was observed with these compounds, the mitochondrial membrane potential was interrupted, and the total ROS production was enhanced. Western blot and immunofluorescence experiments illustrated that these compounds inhibit the expression of markers that are involved in β-catenin and PI3K pathways. Molecular dynamics simulations demonstrated that compound 14a has major hydrophobic interactions and few H-bonding interactions with both PI3K and tankyrase proteins.© 2023 American Chemical Society.