Synthesis and antiproliferative activity of simplified goniofufurone analogues

Bojana Srećo Zelenović, Sanja Grabež, Mirjana Popsavin, Vesna Kojić, Jovana Francuz, Velimir Popsavin


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 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 antitumor activities, provide a suitable basis for the development of new and selective antitumour drugs.


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

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