The lipid extract of an Indonesian Lendenfeldia sp. sponge inhibited hypoxia-induced hypoxia-inducible factor-1 (HIF-1) activation in T47D breast tumor cells. Chromatographic separation yielded the new substituted naphthalene dimer 1, the new furanolipid 2, and three known homoscalarane sesterterpenes, 3-5. Compounds 1 and 3-5 inhibited hypoxia-induced HIF-1 activation (IC50 values: 0.64-6.9 microM), but also reduced the viability of T47D and MDA-MB-231 breast tumor cells. Compound 4 was the most potent and showed a unique tumor cell line selectivity in the NCI 60-cell line panel. The general cytotoxicity of these compounds precluded their further consideration as HIF-1 inhibitors.