A. Chełkowski Institute of Physics and Silesian Center for Education and Interdisciplinary Research, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500, Chorzów, Poland.
Wroclaw School of Information Technology, Ks. M. Lutra 4, 54-239, Wrocław, Poland.
Eur J Med Chem. 2021 Feb 15;212:113032. doi: 10.1016/j.ejmech.2020.113032. Epub 2020 Nov 23.
Terpyridine derivatives are known from their broad application including anticancer properties. In this work we present the newly synthesized 4'-phenyl-2,2':6',2″-terpyridine group with high antiproliferative activity. We suggest that these compounds influence cellular redox homeostasis. Cancer cells are particularly susceptible to any changes in the redox balance because of their handicapped and inefficient antioxidant cellular systems. The antiproliferative activity of the studied compounds was tested on five different cell lines that represent several types of tumours; glioblastoma, leukemia, breast, pancreatic and colon. Additionally, we also tested their selectivity towards normal cells. We performed molecular biology studies in order to detect the response of a cell to its treatment with the compounds that were tested. We looked at the in-depth changes in the proteins and cellular pathways that lead to cell cycle inhibition (G0/G1 and S), and consequently, death on the apoptosis and autophagy pathways. We proved that the studied compounds targeted DNA as well. Special attention was paid to the targets connected with ROS generation.
三吡啶衍生物因其广泛的应用而闻名，包括抗癌特性。在这项工作中，我们提出了新合成的具有高增殖活性的 4'-苯基-2,2':6',2″-三联吡啶基团。我们认为这些化合物会影响细胞氧化还原稳态。由于其受损和低效的抗氧化细胞系统，癌细胞特别容易受到氧化还原平衡任何变化的影响。研究化合物的增殖活性在代表几种肿瘤类型的五种不同细胞系上进行了测试；神经胶质瘤、白血病、乳腺癌、胰腺癌和结肠癌。此外，我们还测试了它们对正常细胞的选择性。我们进行了分子生物学研究，以检测细胞对用测试化合物处理的反应。我们观察了导致细胞周期抑制（G0/G1 和 S）以及凋亡和自噬途径死亡的蛋白质和细胞途径的深入变化。我们证明了研究中的化合物也靶向 DNA。特别关注与 ROS 生成相关的靶点。
