Published August 9, 2017 | Version v.1
Journal article Open

Effects of Terminal Substitution and Iron Coordination on Antiproliferative Activity of l-Proline-salicylaldehyde–Thiosemicarbazone Hybrids

  • 1. Institute of Inorganic Chemistry , University of Vienna, Faculty of Chemistry Währinger S trasse 42, A - 1090, Austria; Institute of Physical Chemistry and Chemical Physics , Slovak University of Technology, Faculty of Chemical and Food Technology , Radlinského 9 , SK - 81237 Bratislava, Slovakia
  • 2. Institute of Inorganic Chemistry , University of Vienna, Faculty of Chemistry , Währinger S trasse 42, A - 1090, Austria
  • 3. Laborato i re National des Champs Magnetiques Intenses - CNRS , 25 Avenue des Martyrs 38042 Grenoble Cedex 9, France
  • 4. Institute for Oncology and Radiology of Serbia Pasterova 14, Belgrade
  • 5. Institute of Physical Chemistry and Chemical Physics , Slovak University of Technology, Faculty of Chemical and Food Technology , Radlinského 9 , SK - 81237 Bratislava, Slovakia
  • 6. Department of Inorganic and Analy tical Chemistry , University of Szeged , Dom ter 7, H - 6720 Szeged, Hungary

Description

A series of five iron(III) complexes, namely [Fe(HL1)Cl2] (1), [Fe(HL2)Cl2]·1.6H2O (1.6H2O), [Fe(HL3)(MeOH)Cl2]·0.5H2O (0.5H2O), [Fe(HL4)(MeOH)Cl2]·0.5H2O (0.5H2O) and [Fe(HL4)(DMF)Cl2]·0.5Et2O·H2O (4′·0.5Et2O·H2O), where H2L1 = l‐proline‐salicylaldehyde–thiosemicarbazone (l‐Pro‐STSC), H2L2 = pyrrolidine‐substituted l‐Pro‐STSC, H2L3 = phenyl‐substituted l‐Pro‐STSC, and H2L4 = naphthyl‐substituted l‐Pro‐STSC, have been synthesized. The two ligand precursors (H2L3 and H2L4) and iron complexes were characterized by elemental analysis, spectroscopic methods (UV/Vis, IR, and NMR), ESI mass spectrometry, cyclic voltammetry, and single‐crystal X‐ray crystallography (1–3 and 4′). Magnetic properties of the five‐coordinate complex 2 and six‐coordinate complex 4 have also been investigated. The antiproliferative activity of the organic hybrids and their iron(III) complexes have been studied in vitro in five human cell lines and one murine cancer cell line, namely HeLa (cervical cancer), FemX (melanoma), A549 (alveolar basal adenocarcinoma), LS‐174 (colon cancer), MDA‐MB‐453 (breast cancer) and MS1 (transformed murine endothelial), as well as in human noncancerous fetal lung fibroblast cell line (MRC‐5). According to the structure–activity relationship, introduction of aromatic groups such as phenyl or naphthyl enhances the cytotoxic potency of the hybrids in the following order H2L1 < H2L2 < H2L3 < H2L4. Coordination of the hybrids to iron(III) improves their antiproliferative activity in the majority of investigated cell lines with exception of H2L3 in LS‐174, H2L4 in MS1, and both H2L3 and H2L4 in FemX cell lines, where an opposite effect was observed.

Notes

This study was financially supported by the Austrian Science Fund (project number P28223 N34), Research and Development Agency of the Slovak Republic under the contracts No. APVV 15-0079 and APVV-15-0053, Scientific Grant Agency of the Slovak Republic (VEGA Project 1/0871/16) and Slovak University of Technology in Bratislava (Young Researcher Grant, M. Milunović, PhD) This work was also supported by Ministry of Education, Science, Research and Sport of the Slovak Republic withinhe Research and Development Operational Program for the project "University Science Park of STU Bratislava", ITMS 26240220084, cofunded by the European Regional Development Fund.

Files

Effects of Terminal Substitution and Iron Coordination on.pdf

Files (1.1 MB)

Additional details

Related works

Has part
1434-1948 (ISSN)