A. Chełkowski Institute of Physics and Silesian Centre for Education and Interdisciplinary Research, University of Silesia, Chorzów, Poland.
Institute of Chemistry, University of Silesia, Katowice, Poland.
Eur J Med Chem. 2020 Mar 1;189:112039. doi: 10.1016/j.ejmech.2020.112039. Epub 2020 Jan 9.
Terpyridine complexes are known for their broad biological activities, of which their anticancer potency is the most extensively studied. Strikingly, free ligand activity has rarely been described in the literature. In this study, a lipophilic derivative of terpyridine 4'-(1-decyl-2,3-triazol-4-yl)phenyl-2,2':6',2″-terpyridine (L) and its complexes were investigated to determine their mechanism of anticancer activity. Our results show that a free ligand expresses the same level of activity on a panel of cancer cells with a low toxicity towards normal fibroblasts as complexes with Cd, Zn or Cu. Breast cancer (MCF-7 cell line) was the most vulnerable for the tested compounds with the IC values in the nanomolar range (IC = 40 nM for L.) The addition of Cu(II) ions increased its activity even further, thus suggesting that ligand exchange and ROS production are the main components of its activity. A cell cycle analysis indicated its inhibition at the G0/G1 phase and the subsequent apoptosis as the cell death mode. A detailed analysis of the protein level that was involved in the aforementioned processes confirmed previous results. Furthermore, the reactive oxygen species generation and DNA intercalation confirmed its cleaving activity.
三联吡啶配合物以其广泛的生物活性而闻名，其中抗癌活性是研究最多的。值得注意的是，游离配体的活性在文献中很少被描述。在这项研究中，研究了三联吡啶 4'-(1-癸基-2,3-三唑-4-基)苯基-2,2':6',2″-三联吡啶（L）的亲脂性衍生物及其配合物，以确定其抗癌活性的机制。我们的结果表明，一种游离配体在一系列癌细胞上表现出相同水平的活性，对正常成纤维细胞的毒性较低，与 Cd、Zn 或 Cu 形成的配合物活性相当。在测试的化合物中，乳腺癌（MCF-7 细胞系）对其最敏感，IC 值在纳摩尔范围内（L 的 IC = 40 nM）。添加 Cu(II)离子进一步提高了其活性，这表明配体交换和 ROS 产生是其活性的主要组成部分。细胞周期分析表明其在 G0/G1 期抑制，随后发生细胞死亡模式的凋亡。对参与上述过程的蛋白质水平的详细分析证实了先前的结果。此外，活性氧的产生和 DNA 嵌入证实了其切割活性。
