Synthesis and biological activity of diisothiocyanate-derived mercapturic acids

Renata Grzywa; Łukasz Winiarski; Mateusz Psurski; Agata Rudnicka; Joanna Wietrzyk; Tadeusz Gajda; Józef Oleksyszyn

doi:10.1016/j.bmcl.2015.11.045

Synthesis and biological activity of diisothiocyanate-derived mercapturic acids

Bioorg Med Chem Lett. 2016 Jan 15;26(2):667-671. doi: 10.1016/j.bmcl.2015.11.045. Epub 2015 Nov 27.

Authors

Renata Grzywa¹, Łukasz Winiarski¹, Mateusz Psurski², Agata Rudnicka¹, Joanna Wietrzyk³, Tadeusz Gajda⁴, Józef Oleksyszyn⁵

Affiliations

¹ Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
² Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland; Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla St. 12, Wrocław 53-114, Poland.
³ Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla St. 12, Wrocław 53-114, Poland.
⁴ Institute of Organic Chemistry, Faculty of Chemistry, Technical University of Lodz, Żeromskiego St. 116, 90-924 Łódź, Poland.
⁵ Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland. Electronic address: jozef.oleksyszyn@pwr.edu.pl.

PMID: 26639764
DOI: 10.1016/j.bmcl.2015.11.045

Abstract

This Letter deals with new non-natural diisothiocyanates, their mercapturic acid derivatives-conjugated with N-acetylcysteine as well as their antiproliferative activity towards human colon cancer cell lines and their inhibitory potency towards histone deacetylase activity. The activity of analysed isothiocyanates is not significantly different than their N-acetylcysteine conjugates. In comparison to simple mono-isothiocyanate analogues, aliphatic diisothiocyanates and their conjugates are much more active than the simple presence of two isothiocyanate functionalities could indicate.

Keywords: Colon cancer cell line; Diisothiocyanate; Histone deacetylase; Mercapturic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine / analogs & derivatives*
Acetylcysteine / pharmacology*
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Colon / drug effects
Colon / pathology
Colonic Neoplasms / drug therapy
Colonic Neoplasms / pathology
Humans
Isothiocyanates / chemistry*
Isothiocyanates / pharmacology*

Substances

Antineoplastic Agents
Isothiocyanates
Acetylcysteine