ABSTRACT
Four compounds (1-4) were isolated from a Hawaiian sponge of the genus Myrmekioderma. Myrmenaphthol A (1) incorporates two unusual elements into an oxidized steroidal core: a naphthyl AB-ring system and a hydroxy group at C-2. A comparison of the experimental and predicted electronic circular dichroism (ECD) spectra of 1 assigned an S configuration to the lone stereocenter (ΔESI = 0.75; similarity factor 0.8137). Known compounds, cinanthrenol A (2), 3,4-dihydroxypregna-5,17-diene-10,2-carbolactone (3), and 3,4-dihydroxypregna-5,20-diene-10,2-carbolactone (4), were also isolated. Despite literature reports of competitive inhibition at nanomolar levels for 2, neither 2 nor the structurally related 1 showed any activity against estrogen receptors at the concentrations tested.
Subject(s)
Porifera/chemistry , Animals , Circular Dichroism , Hawaii , Molecular Structure , Spectrum Analysis/methodsABSTRACT
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 ß-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.
Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Porifera/chemistry , Sesquiterpenes/pharmacology , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Aspartic Acid Endopeptidases/antagonists & inhibitors , Cell Line, Tumor , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Glioma/drug therapy , Glioma/pathology , Hawaii , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/isolation & purification , Heterocyclic Compounds/pharmacology , Humans , Hydroquinones/chemistry , Hydroquinones/isolation & purification , Hydroquinones/pharmacology , Molecular Structure , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Quinones/chemistry , Quinones/isolation & purification , Quinones/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Pancreatic NeoplasmsABSTRACT
Three new ulapualides (3-5) were isolated from egg masses of the nudibranch Hexabranchus sanguineus. The structures of 3-5 were deduced by analyses of physical and spectroscopic data in comparisons with ulapualides A (1) and B (2). Ulapualide C demonstrated submicromolar cytotoxicity against select NCI cell lines (768-0, DU-145, MDA-MB-231, and A549) with the most potent activity against MDA-MB-231 cells (IC50 0.58 µM). Ulapualides A (1) and B (2) were 2- to 4-fold more potent than 3.
Subject(s)
Gastropoda/chemistry , Ovum/chemistry , Oxazoles/isolation & purification , Animals , Drug Screening Assays, Antitumor , Hawaii , Humans , Marine Biology , Molecular Structure , Oxazoles/chemistry , Oxazoles/pharmacologyABSTRACT
Seven new bromotyrosine-derived metabolites, purpuramine M-N (1-2), araplysillin VII-XI (3-7) and six known compounds (8-13) were isolated from an Indonesian sponge belonging to the family Aplysinellidae (Order Verongiida). The structures of the new compounds were determined by extensive NMR experiments and mass spectrometric measurements. These compounds were screened against BACE1 and five cancer cell lines.
Subject(s)
Antineoplastic Agents/pharmacology , Aspartic Acid Endopeptidases/antagonists & inhibitors , Porifera/chemistry , Protease Inhibitors/pharmacology , Tyrosine/analogs & derivatives , Tyrosine/pharmacology , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Isoxazoles/chemistry , Isoxazoles/isolation & purification , Isoxazoles/pharmacology , Mice , NIH 3T3 Cells , Oximes/chemistry , Oximes/isolation & purification , Oximes/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/isolation & purification , Tyrosine/chemistry , Tyrosine/isolation & purificationABSTRACT
New compounds 18-nor-3,17-dihydroxyspongia-3,13(16),14-trien-2-one (1), 18-nor-3,5,17-trihydroxyspongia-3,13(16),14-trien-2-one (2), and spongiapyridine (3) and the known compound 17-hydroxy-4-epi-spongialactone A (4) were isolated from an Indonesian sponge of the genus Spongia. The structures of 1-3 were deduced by analyses of physical and spectroscopic data. Diterpene 3 is unusual, as the D-ring is a pyridyl ring system rather than the standard δ-lactone. The structure elucidation of this compound was complicated by facile exchange of the axial proton at the C-11 methylene with deuterium from methanol-d4. The isolated compounds were tested for biological activity in a battery of in vitro assays (TNF-α-induced NFκB, LPS-induced iNOS, RXR stimulation, quinone reductase 1 induction, aromatase inhibition, TRPM7 ion channels, and aspartic protease BACE1 inhibition). Norditerpene 2 modestly inhibited aromatase with an IC50 of 34 µM and induced quinone reductase 1 activity with a CD (the concentration needed to double the enzymatic response) of 11.2 µM. The remaining isolates were inactive.
Subject(s)
Diterpenes/isolation & purification , Porifera/chemistry , Animals , Diterpenes/chemistry , Diterpenes/pharmacology , Lactones/chemistry , Lipopolysaccharides/pharmacology , Molecular Structure , NAD(P)H Dehydrogenase (Quinone)/drug effects , NF-kappa B/antagonists & inhibitors , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Examination of an active extract of the fruit of Ficus benjamina var. nuda (Miq.) Barrett has led to the isolation of six new isoflavones and two coumarano-chroman-4-ones, along with fifteen known compounds. The structures of the eight new compounds were elucidated on the basis of extensive NMR experiments and mass spectrometric measurements. The inhibitory activity of the compounds on the proteolytic cleavage of amyloid precursor protein by the aspartic protease BACE1 was evaluated. Both coumarano-chroma-4-ones and some isoflavones showed moderate activity in this assay.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Ficus/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Fruit/chemistry , Molecular StructureABSTRACT
Bouillomides A (1) and B (2) are two depsipeptide analogues of dolastatin 13. Isolated from a Guamanian sample of Lyngbya bouillonii, the planar structures were elucidated on the basis of HR-ESI-MS and NMR data, while the absolute configurations were determined by employing functional group conversions, modified Marfey's analysis, and detailed analyses of ROESY correlations. Compounds 1 and 2 selectively inhibited serine proteases elastase (IC(50) = 1.9 µM for both) and chymotrypsin (IC(50) = 0.17 and 9.3 µM, respectively) while showing no inhibition of trypsin (IC(50) > 100 µM).
