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

Abstract

Divergent syntheses 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 the 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 to the 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