Synthesis and antiproliferative activity of simplified goniofufurone analogues

Authors

  • Bojana Srećo Zelenović Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia
  • Sanja Grabež Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia
  • Mirjana Popsavin Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia
  • Vesna Kojić Oncology Institute of Vojvodina, Put Dr. Goldmana 4, 21204 Sremska Kamenica, Serbia
  • Jovana Francuz Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia and Serbian Academy of Sciences and Arts, Kneza Mihaila 35, 11000 Belgrade, Serbia
  • Velimir Popsavin Univ. Novi Sad Faculty of Sciences http://orcid.org/0000-0001-9910-2987

DOI:

https://doi.org/10.2298/JSC200730056S

Keywords:

structure simplification based drug design, goniofufurone mimics, furanolactones, cytotoxicity, Wittig olefination, oxa-Michael ring-closure, SAR analysis

Abstract

Several (+)-goniofufurone analogues with simplified structures were designed, synthesized and evaluated for their in vitro antitumour activity, against a panel of human tumour cell lines. Dephenylated compounds 2 and 3 demonstrated remarkable antitumour activities, in the cultures of K562 and Raji cells with IC50 values in the range of 3.0–9.3 nM. Each of goniofufurone analogues lacking the tetrahydrofuran ring (4, 5 and 6) strongly inhibited the growth of at least one malignant cell line, with IC50 values in the range of 11‑30 nM. Brief structure–activity relationship (SAR) analysis showed that the simplified goniofufurone analogues, designed by removing the phenyl group from C-7, or by opening the THF ring, could show stronger antiproliferative effects compared to control molecules. It is noticeable that analogues 28 are completely inactive with respect to the normal MRC-5 cell line. These find­ings, together with their potent antitumour activities, provide a suitable basis for the development of new and selective antitumour drugs.

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Published

2020-12-23

How to Cite

[1]
B. Srećo Zelenović, S. Grabež, M. Popsavin, V. Kojić, J. Francuz, and V. Popsavin, “Synthesis and antiproliferative activity of simplified goniofufurone analogues”, J. Serb. Chem. Soc., vol. 85, no. 12, pp. 1539–1551, Dec. 2020.

Issue

Section

Organic Chemistry

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