Small molecule glycoconjugates with anticancer activity

Gabriela Pastuch-Gawołek; Katarzyna Malarz; Anna Mrozek-Wilczkiewicz; Marta Musioł; Maciej Serda; Barbara Czaplinska; Robert Musiol

doi:10.1016/j.ejmech.2016.01.061

Small molecule glycoconjugates with anticancer activity

Eur J Med Chem. 2016 Apr 13:112:130-144. doi: 10.1016/j.ejmech.2016.01.061. Epub 2016 Feb 8.

Authors

Gabriela Pastuch-Gawołek¹, Katarzyna Malarz², Anna Mrozek-Wilczkiewicz³, Marta Musioł¹, Maciej Serda², Barbara Czaplinska², Robert Musiol⁴

Affiliations

¹ Silesian University of Technology, Faculty of Chemistry, Chair of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Krzywoustego 4, 44-100 Gliwice, Poland.
² Institute of Chemistry, University of Silesia, 9 Szkolna Street, 40-006 Katowice, Poland.
³ A. Chełkowski Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice, Poland; Silesian Center for Education and Interdisciplinary Research, University of Silesia, 75 Pułku Piechoty 1A, 41-500 Chorzów, Poland.
⁴ Institute of Chemistry, University of Silesia, 9 Szkolna Street, 40-006 Katowice, Poland. Electronic address: robert.musiol@us.edu.pl.

PMID: 26890119
DOI: 10.1016/j.ejmech.2016.01.061

Abstract

Glycoconjugates are combinations of sugar moieties with organic compounds. Due to their biological resemblance, such structures often have properties that are desirable for drugs. In this study we designed and synthesised several glycoconjugates from small molecular quinolines and substituted gluco- and galactopyranosyl amines. Although the parent quinoline compounds were inactive in affordable concentrations, the glycoconjugates that were obtained appeared to be cytotoxic against cancer cells at the micromolar level. When combined with copper ions, their activity increased even further. Their mechanism of action is connected to the formation of reactive oxygen species and the intercalation of DNA.

Keywords: Anticancer; Chelators; Glycoconjugates; Quinoline; Reactive oxygen species.

Publication types

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

MeSH terms

Apoptosis / drug effects
Coordination Complexes / chemistry
Coordination Complexes / pharmacology
Copper / chemistry
Copper / pharmacology
DNA / metabolism
Glycoconjugates / chemistry*
Glycoconjugates / pharmacology*
HCT116 Cells
Humans
Intercalating Agents / chemistry*
Intercalating Agents / pharmacology*
Neoplasms / drug therapy
Neoplasms / metabolism
Quinolines / chemistry*
Quinolines / pharmacology*
Reactive Oxygen Species / metabolism
Zinc / chemistry
Zinc / pharmacology

Substances

Coordination Complexes
Glycoconjugates
Intercalating Agents
Quinolines
Reactive Oxygen Species
Copper
DNA
quinoline
Zinc