Inhibitors of Rho-kinase modulate amyloid-β (Aβ) secretion but lack selectivity for Aβ42
Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit production of the amyloidogenic Abeta42 peptide, presumably by direct modulation of gamma-secretase activity. A recent report indicated that NSAIDs could reduce Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho kinase (ROCK) mimicked the effects of Abeta42-lowering NSAIDs. To investigate whether Abeta42 reduction is a common property of ROCK inhibitors, we tested commercially available compounds in cell lines that were previously used to demonstrate the Abeta42-lowering activity of NSAIDs. Surprisingly, we found that two ROCK inhibitors reduced total Abeta secretion in a dose-dependent m…
A Synthetic Glycopeptide Vaccine for the Induction of a Monoclonal Antibody that Differentiates between Normal and Tumor Mammary Cells and Enables the Diagnosis of Human Pancreatic Cancer.
In studies within the realm of cancer immunotherapy, the synthesis of exactly specified tumor-associated glycopeptide antigens is shown to be a key strategy for obtaining a highly selective biological reagent, that is, a monoclonal antibody that completely differentiates between tumor and normal epithelial cells and specifically marks the tumor cells in pancreas tumors. Mucin MUC1, which is overexpressed in many prevalent cancers, was identified as a promising target for this strategy. Tumor-associated MUC1 differs significantly from that expressed by normal cells, in particular by altered glycosylation. Structurally defined tumor-associated MUC1 cannot be isolated from tumor cells. We synt…
Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies.
Abstract Fermentation of the marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3–8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH4)2SO4 that resulted in the accumulation of three further known compounds (9–11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted fo…
Didymellanosine, a new decahydrofluorene analogue, and ascolactone C from Didymella sp. IEA-3B.1, an endophyte of Terminalia catappa
Didymellanosine (1), the first analogue of the decahydrofluorene-class of natural products bearing a 13-membered macrocyclic alkaloid conjugated with adenosine, and a new benzolactone derivative, ascolactone C (4) along with eight known compounds (2, 3, 5–10), were isolated from a solid rice fermentation of the endophytic fungus Didymella sp. IEA-3B.1 derived from the host plant Terminalia catappa. In addition, ascochitamine (11) was obtained when (NH4)2SO4 was added to rice medium and is reported here for the first time as a natural product. Didymellanosine (1) displayed strong activity against the murine lymphoma cell line L5178Y, Burkitt's lymphoma B cells (Ramos) and adult lymphoblastic…