2. Academic Validation
  3. New derivatives of 4'-phenyl-2,2':6',2″-terpyridine as promising anticancer agents

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

  • Eur J Med Chem. 2021 Feb 15:212:113032. doi: 10.1016/j.ejmech.2020.113032.
Katarzyna Malarz 1,  Dawid Zych 2,  Robert Gawecki 3,  Michał Kuczak 4,  Robert Musioł 5,  Anna Mrozek-Wilczkiewicz 6
Affiliations

Affiliations

  • 1 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. Electronic address: katarzyna.malarz@us.edu.pl.
  • 2 Wroclaw School of Information Technology, Ks. M. Lutra 4, 54-239, Wrocław, Poland.
  • 3 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.
  • 4 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; Institute of Chemistry, University of Silesia in Katowice, Szkolna 9, 40-006, Katowice, Poland.
  • 5 Institute of Chemistry, University of Silesia in Katowice, Szkolna 9, 40-006, Katowice, Poland.
  • 6 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. Electronic address: anna.mrozek-wilczkiewicz@us.edu.pl.
PMID: 33261897 DOI: 10.1016/j.ejmech.2020.113032
Abstract

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.

Keywords

Anticancer activity; Metal chelators; Reactive oxygen species; Terpyridine.

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