School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Molecules. 2022 Mar 18;27(6):1970. doi: 10.3390/molecules27061970.
Three benzoxanthone derivatives were synthesized through a new photochemical strategy. The in vitro cytotoxic activity of these compounds was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and their partition coefficients (log) were measured by shake flask method. The p values of the compounds were detected by potentionmetric titration. The interaction of the compounds with calf thymus DNA (CT-DNA) was investigated by electronic absorption, luminescence spectra and viscosity. A molecular docking analysis was performed. The antitumor efficacy of the compounds was evaluated by cell apoptosis, cell cycle arrest, intracellular Ca concentrations and reactive oxygen species (ROS) levels. The mitochondrial membrane potential was assayed using JC-1 (5,5',6,6'-tetrachloro-1,1,3',3'-tetraethyl-imidacarbocyanine iodide) as the fluorescence probe. The expression of Bcl-2 family protein, caspase 3 and poly ADP-ribose polymerase (PARP) was explored by western blot. The results showed that the compounds induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. This work provides an efficient approach to synthesize benzoxanthone derivatives, and is helpful for understanding the apoptotic mechanism.
三种苯并氧杂蒽酮衍生物通过一种新的光化学策略合成。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐 (MTT) 测定法评估这些化合物的体外细胞毒性活性，并通过振摇瓶法测量它们的分配系数 (log)。通过电位滴定法检测化合物的 p 值。通过电子吸收、发光光谱和粘度研究了化合物与小牛胸腺 DNA (CT-DNA) 的相互作用。进行了分子对接分析。通过细胞凋亡、细胞周期阻滞、细胞内 Ca 浓度和活性氧 (ROS) 水平评估化合物的抗肿瘤功效。使用 JC-1（5,5',6,6'-四氯-1,1,3',3'-四乙基-碘化咪唑羰花青）作为荧光探针测定线粒体膜电位。通过 Western blot 探索 Bcl-2 家族蛋白、caspase 3 和聚 ADP-核糖聚合酶 (PARP) 的表达。结果表明，这些化合物通过 ROS 介导的线粒体功能障碍途径诱导细胞凋亡。这项工作提供了一种合成苯并氧杂蒽酮衍生物的有效方法，有助于了解凋亡机制。
