Novel (−)-goniofufurone mimics: synthesis, antiproliferative activity and SAR analysis

Bojana Srećo Zelenović, Sladjana Kekezović, Mirjana Popsavin, Vesna Kojić, Goran Benedeković, Velimir Popsavin

Abstract


Divergent synthesis of novel (−)-goniofufurone mimics with an alkoxymethyl group as the side chain have been accomplished from d-glucose in nine synthetic steps and in overall yields 6.7– 8.7%. Their in vitro antiproliferative activity was evaluated against eight human tumour cell lines as well as a single normal cell line. All analogues demonstrated powerful to good antiproliferative effects toward all malignant cell lines under evaluation. Against HL-60 cell line, all mimics showed increased activities being 27- to 1604-fold more potent than the lead compound, (−)-goniofufurone. Remarkably, the majority of synthesized analogues displayed higher or similar activity as commercial antitumour agent doxorubicin (DOX) against A549 cell line. The most potent compound exhibited 196-fold stronger cytotoxicity than DOX, in the culture of this cell line.

Keywords


D-glucose; antitumour agents; goniofufurone mimics; cytotoxic lactones, structure-activity relationships

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DOI: https://doi.org/10.2298/JSC190912104S

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