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Iron chelates in the anticancer therapy

Wojciech Szlasa, Martyna Gachowska, Karolina Kiszka, Katarzyna Rakoczy, Aleksander Kiełbik, Kamila Wala, Julia Puchała, Katarzyna Chorążykiewicz, Jolanta Saczko, and Julita Kulbacka

Faculty of Medicine, Wrocław Medical University, Wrocław, Poland

 

E-mail: julita.kulbacka@umw.edu.pl

Received: 23 September 2021  Accepted: 29 November 2021

Abstract:

Iron plays a significant role in the metabolism of cancer cells. In comparison with normal cells, neoplastic ones exhibit enhanced vulnerability to iron. Ferric ions target tumor via the ferroptotic death pathway—a process involving the iron-mediated lipid oxidation. Ferric ion occurs in complex forms in the physiological conditions. Apart from iron, ligands are the other factors to affect the biological activity of the iron complexes. In recent decades the role of iron chelates in targeting the growth of the tumor was extensively examined. The ligand may possess a standalone activity to restrict cancer’s growth. However, a wrong choice of the ligand might lead to the enhanced cancer cell’s growth in in vitro studies. The paper aims to review the role of iron complex compounds in the anticancer therapy both in the experimental and clinical applications. The anticancer properties of the iron complex rely both on the stability constant of the complex and the ligand composition. When the stability constant is high, the properties of the drug are unique. However, when the stability constant remains low, both components—ferric ions and ligands, act separately on the cells. In the paper we show how the difference in complex stability implies the action of ligand and ferric ions in the cancer cell. Iron complexation strategy is an interesting attempt to transport the anticancer Fe2+/3+ ions throughout the cell membrane and release it when the pH of the microenvironment changes. Last part of the paper summarizes the results of clinical trials and in vitro studies of novel iron chelates such as: PRLX 93,936, Ferumoxytol, Talactoferrin, DPC, Triapine, VLX600, Tachypyridine, Ciclopiroxamine, Thiosemicarbazone, Deferoxamine and Deferasirox.

Keywords: Iron chelates; Iron complex; Cancer; Chemotherapy; Diet supplements

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-021-02001-2

 

Chemical Papers 76 (3) 1285–1294 (2022)

Wednesday, May 22, 2024

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