New derivatives of 4 '-phenyl-2,2 ':6 ',2 ''-terpyridine as promising anticancer agents

摘要

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 anti-proliferative 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. (C) 2020 Elsevier Masson SAS. All rights reserved.