Lithothamnin A (1) is a new bastadin-like metabolite and represents the first report of this class of molecules from the red alga Lithothamnion fragilissimum. Lithothamnin A contains several novel structural features that distinguish it from other bastadins. These unique structural features include novel aromatic substitution patterns and the presence of a meta-meta linkage between aromatic rings, in addition to the meta-para linkage seen in the bastadins. Lithothamnin A is modestly cytotoxic in a panel of six human tumor cell lines.
Renal or kidney cancer accounts for about 3% of all cancer cases reported each year in the US. Molecular signatures that define the cancer, such as the loss of functional VHL, are found in both sporadic and familial cases of cancer. In clear cell renal cancer, the transcription factor HIF-2α has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2α. Screening of the NCI’s Natural Product Extract Repository resulted in the identification of 10 sponge extracts from which 12 compounds were isolated. The biological evaluation of these compounds will be discussed including evaluation of HIF-1α vs. HIF-2αselectively and the isolated compounds’ effects on mRNA from several pathways regulated by HIF.
A reinvestigation of extracts of the endemic South African intertidal limpet Trimusculus costatus yielded the known labdane diterpenes 6beta,7alpha-diacetoxylabda-8,13 E-dien-15-ol ( 1) and 2alpha,6beta,7alpha-triacetoxylabda-8,13 E-dien-15-ol ( 2) and three new metabolites, 6beta,7alpha,15-triacetoxylabda-8,13 E-diene ( 3), 3alpha,11-dihydroxy-9,11-seco-cholest-4,7-dien-6,9-dione ( 4), and cholest-7-en-3,5,7-triol ( 5). Chiral derivatization and X-ray analysis were used to confirm the labdane absolute configuration of 2. Compounds 1, 2 and 4 exhibited moderate activity (3-25 microM) against the WHCO1 human esophageal cancer cell line.
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