Bioactive furonaphtoquinones from Tabebuia barbata (Bignoniaceae)

Tabebuia barbata (E. Mey) Sandw. (Bignoniaceae), locally known as "palo de arco", is indigenous to the upper Orinoco and Amazonas rivers. Brine shrimp lethality-directed fractionation and extensive column chromatography, normal-phase preparative TLC and normal-phase HPLC separation of the ethanol extract of the bark of this previously uninvestigated species has led to the isolation of five active compounds 1-5. The combined spectral evidence (UV, IR, 1H and 13C NMR and mass) identified these compounds as naphthoquinones. These compounds, characterized as lapachol (1), 2-acetylnaphtho-[2,3-b]-furan-4,9-dione (2), 2-acetyl-5-hydroxy-naphtho-[2,3-b]-furan-4,9-dione (3), 2-acetyl-8-hydroxy-naphtho-[2,3-b]-furan-4,9-dione (4), and (+)-8-hydroxy-2(1-hydroxy-ethyl) naphtho-[2,3-b]-furan-4,9-dione (5), were reported previously from other species of the genus Tabebuia but not from T. barbata. Compounds 2-5, reference adriamycin, were significantly cytotoxic against A-549 human lung adeno-carcinoma, MCF-7 human breast carcinoma, and HT-29 human colon carcinoma cells. The compounds isolated (1-5) were also shown to be inhibitors of electron transport in rat liver mitochondria, reference to rotenone, with IC50 values in the range of 15 microM to 82.5 microM. In addition, this study demonstrated that screening and activity-directed fractionation, using brine shrimp lethality as a simple and inexpensive bioassay, can effectively lead to potential antitumor compounds.