Cytotoxic metabolites from an Indonesian sponge Lendenfeldia sp.
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.
Dai
Jingqiu
J
Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Mississippi 38677-1848, USA.
Liu
Yang
Y
Zhou
Yu-Dong
YD
Nagle
Dale G
DG
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D007214:Indonesia; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*; D054830:Sesterterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D054830:Sesterterpenes; D008156:Luciferases