In this study, five biflavonoids (1 to 5) have been isolated from the leaves of the Indonesian plant Araucaria hunsteinii K. Schum. The structures of biflavonoids were determined using various techniques, including one- and two-dimensional nuclear magnetic resonance, infrared, ultraviolet-visible, and mass spectrometric investigations. These compounds were identified as derivatives of cupressuflavone, amentoflavone, and agathisflavone. The cytotoxic potential of the isolated biflavonoids was evaluated against cancer cell lines, the cervical HeLa cancer cells, and the human breast Michigan Cancer Foundation-7 (MCF-7). All compounds were first isolated from this species, and compound 1 was first recognized as a member of the genus Araucaria. Compounds 1, 2, and 3 inhibition concentration 50 (IC50 of 11.54 ± 3.4, 3.40 ± 0.3, and 2.14 ± 0.6 μM, respectively) showed very active inhibition with 3 having the best activity against inhibition of MCF-7 cells. In addition, 2 and 3 (IC50 of 1.42 ± 1.1 and 11.03 ± 2.9 μM, respectively) also showed very strong inhibitory effects, with 2 having the best inhibitory activity against HeLa cancer cells. All compounds have a higher IC50 value compared to epirubicin-HCl and napradox-50 (IC50 0.55 ± 0.2 and 0.35 ± 0.03 μM, respectively), indicating that all samples have lower activity than the positive controls. The structure-activity relationship analysis of these isolated metabolites shows that cupressuflavone and amentoflavone are the two most promising biflavonoid skeletons for developing anticancer drugs. The methoxy groups of the biflavonoid moiety modify their inhibitory effects on MCF-7 and HeLa cancer cells, and compounds 2 and 3 work best as inhibitors against HeLa cancer cells and MCF-7 cells, respectively, because of their hydroxyl position at C4′, 4?′, and 7?. This study has revealed the potency of cupressuflavone and amentoflavone-derived compounds that potentially developed further as active constituents in cancer medication.
Key words: Araucaria Hunsteinii, Biflavonoids, MCF-7 and HeLa Cancer Cells, SAR
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