2. Academic Validation
  3. Synthesis and antiproliferative activity of goniobutenolides A and B, 5-halogenated crassalactone D derivatives and the corresponding 7-epimers

Synthesis and antiproliferative activity of goniobutenolides A and B, 5-halogenated crassalactone D derivatives and the corresponding 7-epimers

  • Eur J Med Chem. 2016 Jan 27:108:594-604. doi: 10.1016/j.ejmech.2015.12.011.
Ivana Kovačević 1,  Mirjana Popsavin 1,  Goran Benedeković 1,  Vesna Kojić 2,  Dimitar Jakimov 2,  Marko V Rodić 1,  Tatjana Srdić-Rajić 3,  Gordana Bogdanović 2,  Vladimir Divjaković 4,  Velimir Popsavin 5
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, Put Doktora Goldmana 4, 21204, Sremska Kamenica, Serbia.
  • 3 Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
  • 4 Department of Physics, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 4, 21000 Novi Sad, Serbia.
  • 5 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: 26720155 DOI: 10.1016/j.ejmech.2015.12.011
Abstract

A new synthesis of goniobutenolides A (1) and B (2) and the corresponding 7-epimers has been achieved starting from diacetone d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with Z-selective Wittig (or Horner-Wadsworth-Emmons) olefination, followed by successive γ-lactonisation and β-elimination. The above-mentioned unsaturated lactones were then converted to the corresponding 5-halogenated crassalactone D derivatives by using the appropriate haloetherification protocol. The most of synthesized compounds exhibited potent cytotoxic activities against a panel of tumour cell lines. The main structural features responsible for their antitumour potency have been revealed by means of SAR analysis. Flow cytometry data suggested that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by Apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of semi-quantitative Western blot analysis indicate that the most of synthesized compounds induce Apoptosis in a caspase-dependent manner.

Keywords

Antitumour activity; Apoptosis; Crassalactone D; Goniobutenolide A; Goniobutenolide B; Haloetherification; Structure-activity relationships.

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