Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents

Anna Gliszczyńska; Natalia Niezgoda; Witold Gładkowski; Marta Czarnecka; Marta Świtalska; Joanna Wietrzyk

doi:10.1371/journal.pone.0157278

Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents

PLoS One. 2016 Jun 16;11(6):e0157278. doi: 10.1371/journal.pone.0157278. eCollection 2016.

Authors

Anna Gliszczyńska¹, Natalia Niezgoda¹, Witold Gładkowski¹, Marta Czarnecka¹, Marta Świtalska², Joanna Wietrzyk²

Affiliations

¹ Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
² Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Experimental Oncology, Weigla 12, 53-114 Wrocław, Poland.

Abstract

The synthesis of novel phosphatidylcholines with geranic and citronellic acids in sn-1 and sn-2 positions is described. The structured phospholipids were obtained in high yields (59-87%) and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MV4-11, A-549, MCF-7, LOVO, LOVO/DX, HepG2 and also towards non-cancer cell line BALB/3T3 (normal mice fibroblasts). The phosphatidylcholines modified with monoterpene acid showed a significantly higher antiproliferative activity than free monoterpene acids. The highest activity was observed for the terpene-phospholipids containing the isoprenoid acids in sn-1 position of phosphatidylcholine and palmitic acid in sn-2.

MeSH terms

A549 Cells
Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Hep G2 Cells
Humans
Inhibitory Concentration 50
MCF-7 Cells
Mice
Monoterpenes / chemistry
NIH 3T3 Cells
Organ Specificity
Palmitic Acid / chemistry
Phosphatidylcholines / chemical synthesis*
Phosphatidylcholines / pharmacology
Structure-Activity Relationship
Terpenes / chemistry

Substances

Antineoplastic Agents
Monoterpenes
Phosphatidylcholines
Terpenes
Palmitic Acid

Grants and funding

This project was financed by National Science Center of Poland no. 2013/09/D/NZ9/02457. Publication was supported by Wroclaw Centre of Biotechnology, programme The Leading National Research Centre (KNOW) for years 2014-2018 (http://know.wroc.pl).