New glutathione peroxidase mimetics-Insights into antioxidant and cytotoxic activity

Agata J Pacuła; Katarzyna B Kaczor; Angelika Wojtowicz; Jędrzej Antosiewicz; Anna Janecka; Angelika Długosz; Tomasz Janecki; Jacek Ścianowski

doi:10.1016/j.bmc.2016.10.018

New glutathione peroxidase mimetics-Insights into antioxidant and cytotoxic activity

Bioorg Med Chem. 2017 Jan 1;25(1):126-131. doi: 10.1016/j.bmc.2016.10.018. Epub 2016 Oct 18.

Authors

Agata J Pacuła¹, Katarzyna B Kaczor², Angelika Wojtowicz², Jędrzej Antosiewicz², Anna Janecka³, Angelika Długosz³, Tomasz Janecki⁴, Jacek Ścianowski⁵

Affiliations

¹ Department of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, Poland.
² Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, 1 Debinki Street, 80-211 Gdansk, Poland.
³ Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
⁴ Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
⁵ Department of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarin Street, 87-100 Torun, Poland. Electronic address: jsch@chem.umk.pl.

PMID: 28029457
DOI: 10.1016/j.bmc.2016.10.018

Abstract

A series of N-alkyl benzisoselenazol-3(2H)-ones has been obtained and transformed to corresponding diselenides by the reduction with sodium borohydride. Additionally, efficient methodology for the oxidative Se-N bond formation by potassium iodate has been presented, new conversion of diselenide to benzisoselenazolone was observed. The GPx-like activity of all synthetized derivatives has been evaluated by NMR. N-Allyl diselenide was up to five times better antioxidant than ebselen. Anticancer capacity towards MCF7 and DU145 cancer cells has been also tested. The highest antiproliferative activity was obtained for N-cyclohexyl benzisoselenazolone.

Keywords: Antioxidant activity; Benzisoselenazolones; Cytotoxicity; Diselenides.

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Antioxidants / chemistry*
Antioxidants / pharmacology*
Azoles / chemistry*
Azoles / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Glutathione Peroxidase / chemistry*
Glutathione Peroxidase / pharmacology*
Humans
Isoindoles
Organoselenium Compounds / chemistry*
Organoselenium Compounds / pharmacology*

Substances

Antineoplastic Agents
Antioxidants
Azoles
Isoindoles
Organoselenium Compounds
ebselen
Glutathione Peroxidase