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The natural products from plants still remain an important source of pharmaceuticals. In the current study, bark and wood extracts of Ficus elastica aerial roots were screened for anti-cancer activity. Three new compounds, ficusamide, ficusoside and elasticoside, were isolated from the bark of aerial roots, together with nine known compounds. Three new compounds, elasticamide, elastiquinone and ficusoside B, together with four known compounds, were isolated from the wood of aerial roots. The structures of the new compounds were established by means of extensive spectroscopic analyses and by data with those reported for structurally related molecules. The isolated compounds were afterwards evaluated for their anti-proliferative effect on six human cancer cell lines using colorimetric MTT assay. Most notably, elastiquinone showed cytotoxic activity with IC50 = 14 µM against B16F10 melanoma cells, whereas the peracetylated form of ficusoside B displayed the lowest IC50 value (11 µM)against U373n glioma cell lines. The results of this investigation demonstrate that F. elastica might be a potential source for identifying new compounds with potent anti-proliferative activity.