The natural products from plants still remain an important source of pharmaceuticals. In the current study, methanolic wood extracts of Ficus elastica Roxb. ex Hornem. (Moraceae) aerial roots were screened for anti-cancer activity. Using bioassay-guided fractionation, three new compounds, elasticamide ( 1 ), elastiquinone ( 2 ) and ficusoside B ( 3 ), together with four known compounds, were isolated. The structures of the new compounds were established by means of extensive spectroscopic analyses (1D and 2D NMR, HR-ESI-MS, as well as IR and UV) and by comparison of their spectroscopic 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 (U373n and Hs683 glioblastoma, MCF7 and A549 NSCLC carcinoma, and B16F10 and SK-MEL-28 melanoma) using colorimetric MTT assay. Most notably, elastiquinone ( 2 ) showed cytotoxic activity with IC 50 = 14 μM against B16F10 melanoma cells, whereas the peracetylated form of ficusoside B ( 3a ) displayed the lowest IC 50 value (11 μM) against U373n glioma cell lines. Elasticamide ( 1) and ficusoside B ( 3) exhibited a weak cytotoxicity with IC 50 values ≥ 88 μM. The results of this investigation demonstrate that the wood of F. elastica aerial roots might be a potential source for identifying new compounds with potent anti-proliferative activity. [ABSTRACT FROM AUTHOR]