2. Academic Validation
  3. Design, synthesis and in vitro antitumour activity of new goniofufurone and 7-epi-goniofufurone mimics with halogen or azido groups at the C-7 position

Design, synthesis and in vitro antitumour activity of new goniofufurone and 7-epi-goniofufurone mimics with halogen or azido groups at the C-7 position

  • Eur J Med Chem. 2017 Mar 10:128:13-24. doi: 10.1016/j.ejmech.2017.01.024.
Jovana Francuz 1,  Ivana Kovačević 1,  Mirjana Popsavin 1,  Goran Benedeković 1,  Bojana Srećo Zelenović 1,  Vesna Kojić 2,  Dimitar Jakimov 2,  Lidija Aleksić 2,  Gordana Bogdanović 2,  Tatjana Srdić-Rajić 3,  Eva Lončar 4,  Marko V Rodić 1,  Vladimir Divjaković 5,  Velimir Popsavin 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
  • 2 Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put Dr Goldmana 4, 21204 Sremska Kamenica, Serbia.
  • 3 Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
  • 4 Faculty of Technology, University of Novi Sad, Bulevar Cara Lazara 1, 21000 Novi Sad, Serbia.
  • 5 Department of Physics, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
  • 6 Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: velimir.popsavin@dh.uns.ac.rs.
PMID: 28135634 DOI: 10.1016/j.ejmech.2017.01.024
Abstract

A series of new antitumour lactones containing the [3.3.0] bicyclic furano-lactone core and the halogen or azido group at the C-7 position have been designed, synthesized, and evaluated for their in vitro antitumour activity against a panel of human tumour cell lines. Some of the analogues displayed powerful antiproliferative effects to certain human tumour cells, but all of them were devoid of any cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural features of these lactones that may affect their antiproliferative activity. These are: the nature of substituent present at the C-7 position, stereochemistry at the C-7 position, the absence of phenyl group at the C-7 position. Flow cytometry data indicate that the cytotoxic effects of the synthesized analogues in a culture of K562 cells are mediated by Apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of Western blot analysis suggested that the most of synthesized compounds induce Apoptosis in K562 cells in caspase-dependent way.

Keywords

Analogues; Antitumour activity; Detection of apoptosis; Halogen isosteres; Structure-activity relationships; Styryl lactones.

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