Synthesis of vitamin E and aliphatic lipid vanadium(IV) and (V) complexes, and their cytotoxic properties

Ioanna Hadjiadamou; Manolis Vlasiou; Smaragda Spanou; Yannis Simos; George Papanastasiou; Evangelos Kontargiris; Irida Dhima; Vasilios Ragos; Spyridon Karkabounas; Chryssoula Drouza; Anastasios D Keramidas

doi:10.1016/j.jinorgbio.2020.111074

Synthesis of vitamin E and aliphatic lipid vanadium(IV) and (V) complexes, and their cytotoxic properties

J Inorg Biochem. 2020 Jul:208:111074. doi: 10.1016/j.jinorgbio.2020.111074. Epub 2020 May 4.

Affiliations

¹ Department of Chemistry, University of Cyprus, Nicosia 1678, Cyprus.
² Cyprus University of Technology, Department of Agricultural Production, Biotechnology and Food Science, Limassol 3036, Cyprus.
³ Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece.
⁴ Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece; Maxillofacial Surgery, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.
⁵ Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece; Department of Nursing, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece.
⁶ Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece. Electronic address: skarkabounas@gmail.com.
⁷ Cyprus University of Technology, Department of Agricultural Production, Biotechnology and Food Science, Limassol 3036, Cyprus. Electronic address: chryssoula.drouza@cut.ac.cy.
⁸ Department of Chemistry, University of Cyprus, Nicosia 1678, Cyprus. Electronic address: akeramid@ucy.ac.cy.

PMID: 32497827
DOI: 10.1016/j.jinorgbio.2020.111074

Abstract

Novel vitamin E chelate derivatives and their V^IV/V complexes have been synthesized and characterized, and their anticancer properties have been evaluated. The new complexes have been designed to exhibit enhanced cytotoxicity by combining high lipophilicity with the properties of vanadium to induce the formation of reactive oxygen species (ROS). In particular, the β-tocopherol derivatives with iminodiethanol (β-tocDEA) and dipicolylamine (β-tocDPA) as well their V^V and V^IV complexes, [V^VO(β-tocDEA] and [V^IVO(β-tocDPA] have been synthesized and characterized by Nuclear Magnetic Resonance (NMR), Ultra Violet-Visible (UV-Vis) and Electron Paramagnetic Resonance (EPR) spectroscopies. Although the β-tocopherol compounds exhibit antioxidant activity their complexes induce formation of radicals. In addition, two vanadium amphiphilic complexes of 2,2'-((2-hydroxyoctadecyl)azanediyl)bis(ethan-1-ol) (C18DEA) and 1-(bis(pyridin-2-ylmethyl)amino)octadecan-2-ol (C18DPA) known to activate O₂ and produce ROS were synthesized and characterized (C. Drouza, A. Dieronitou, I. Hadjiadamou, M. Stylianou, J. Agric. Food. Chem., vol. 65, 2017, pp. 4942-4951). The four amphiphilic vanadium complexes exhibit enhanced hydrolytic stability. All compounds found to be cytotoxic for cancer cells exhibiting activity similar or higher to cis-platin.

Keywords: Cytotoxic; Radicals; Tocopherol; Vanadium; Vitamin E.

MeSH terms

Coordination Complexes* / chemical synthesis
Coordination Complexes* / chemistry
Coordination Complexes* / pharmacokinetics
Coordination Complexes* / pharmacology
Cytotoxins* / chemical synthesis
Cytotoxins* / chemistry
Cytotoxins* / pharmacokinetics
Cytotoxins* / pharmacology
HEK293 Cells
HeLa Cells
Humans
Lipids* / chemical synthesis
Lipids* / chemistry
Lipids* / pharmacokinetics
Lipids* / pharmacology
Neoplasms* / drug therapy
Neoplasms* / metabolism
Neoplasms* / pathology
Vanadium* / chemistry
Vanadium* / pharmacokinetics
Vanadium* / pharmacology
Vitamin E* / chemical synthesis
Vitamin E* / chemistry
Vitamin E* / pharmacokinetics
Vitamin E* / pharmacology

Substances

Coordination Complexes
Cytotoxins
Lipids
Vanadium
Vitamin E