Abstract
Several known sesquiterpenoid quinones and quinols (1–9), and kauamide (10), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans. The planar structure of 10 was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey’s analysis of the N-MeLeu residue, respectively. Compounds 1 and 3 showed moderate inhibition of β-secretase 1 (BACE1), whereas 1–9 exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds 1–2 and 4–7 were also active against human pancreatic carcinoma (Panc-1) cells.
Highlights
Since the discovery of unusual nucleosides from the sponge Tethya crypta by Bergmann and Feeney in the early 1950s [1], various classes of biologically-active secondary metabolites, including alkaloids, peptides, steroids and terpenes, have been isolated from marine sponges [2]
Sponge metabolites are of considerable pharmaceutical interest and they span a wide range of activities, such as anticancer, anti-inflammatory, antiviral, and antibacterial. These include three compounds that have been approved by the U.S Food and Drug Administration (FDA) as clinical drugs [3]
In our quest to discover new inhibitors of BACE1 from marine organisms, it was found that an extract of D. elegans displayed activity against the enzyme in our in vitro assay system
Summary
Since the discovery of unusual nucleosides from the sponge Tethya crypta by Bergmann and Feeney in the early 1950s [1], various classes of biologically-active secondary metabolites, including alkaloids, peptides, steroids and terpenes, have been isolated from marine sponges [2]. Sponge metabolites are of considerable pharmaceutical interest and they span a wide range of activities, such as anticancer, anti-inflammatory, antiviral, and antibacterial These include three compounds that have been approved by the U.S Food and Drug Administration (FDA) as clinical drugs [3]. Sponges of the genus Dactylospongia are well-known producers of sesquiterpenoid quinones and hydroquinones, including ilimaquinone [6,7,8], nakijiquinones [9,10,11], puupehenol [12] and others These secondary metabolites, which possess either a drimane or a 4,9-friedo-rearranged skeleton, are known to exhibit various biological effects, such as cytotoxicity, antitumor, antiviral and anti-inflammatory activities [10,13,14,15,16]. We describe the structure elucidation of the new heterocyclic compound, and results from bioassays involving BACE1, human glioma (U251MG) and human pancreatic carcinoma (Panc-1) cells
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