Institute of Advanced Synthesis, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.
Yangtze River Delta Research Institute, Northwestern Polytechnical University, Taicang, Jiangsu 215400, China.
Nano Lett. 2021 Feb 10;21(3):1384-1391. doi: 10.1021/acs.nanolett.0c04134. Epub 2021 Jan 19.
We report here a novel class of cation transporters with extreme simplicity, opening a whole new dimension of scientific research for finding small molecule-based cation transporters for therapeutic applications. Comprising three modular components (a headgroup, a flexible alkyl chain-derived body, and a crown ether-derived foot for ion binding), these transporters efficiently (EC = 0.18-0.41 mol % relative to lipid) and selectively (K/Na selectivity = 7.0-9.5) move K ions across the membrane. Importantly, the most active (EC = 0.18-0.22 mol %) and highly selective series of transporters A12, B12, and C12 concurrently possess potent anticancer activities with IC values as low as 4.35 ± 0.91 and 6.00 ± 0.13 μM toward HeLa and PC3 cells, respectively. Notably, a mere replacement of the 18-crown-6 unit in the structure with 12-crown-4 or 15-crown-5 units completely annihilates the cation-transporting ability.
我们在这里报告了一类新型的阳离子转运体，其结构极其简单，为寻找基于小分子的阳离子转运体用于治疗应用开辟了全新的科学研究维度。这些转运体由三个模块化组件（一个头基、一个由柔性烷基链衍生的主体和一个冠醚衍生的用于离子结合的脚）组成，它们能够高效（EC=0.18-0.41 mol%相对于脂质）和选择性（K+/Na+选择性=7.0-9.5）地跨膜转运 K+离子。重要的是，最活跃（EC=0.18-0.22 mol%）和高度选择性的 A12、B12 和 C12 系列转运体同时具有强大的抗癌活性，对 HeLa 和 PC3 细胞的 IC 值分别低至 4.35±0.91 和 6.00±0.13 μM。值得注意的是，在结构中仅将 18-冠-6 单元替换为 12-冠-4 或 15-冠-5 单元，就完全消除了阳离子转运能力。
