Synthesis and Bioevaluation of Novel Oxa-Caged Garcinia Xanthones as Anti-Tumour Agents

Abstract

Gambogic acid (GA), a special category of Garcinia xanthones, has attracted great attention owing to its striking bioactivities and unique structure. To further explore its structure–activity relationship, we prepared seven novel oxa-caged Garcinia xanthones that were for the first time varied at the C-2 position of B ring and at the C-21/22 or C-23 position of the prenyl group in the caged scaffold. Some compounds exhibited strong anti-proliferation activities in different cancer cell lines. Particularly, compound 8 showed more potent cytotoxic activity and better selectivity towards the A549 cell line than GA. Oxa-caged xanthones 8 was identified as an A549 cell apoptosis inducer through observations of morphological changes and Annexin-V/PI double-staining assay. Additionally, the structure–activity relationships of these new analogues were discussed.