Sclerotiorin stabilizes the assembly of nonfibrillar Abeta42 oligomers with low toxicity, seeding activity, and Beta-sheet content was written by Wiglenda, Thomas;Groenke, Nicole;Hoffmann, Waldemar;Manz, Christian;Diez, Lisa;Buntru, Alexander;Brusendorf, Lydia;Neuendorf, Nancy;Schnoegl, Sigrid;Haenig, Christian;Schmieder, Peter;Pagel, Kevin;Wanker, Erich E.. And the article was included in Journal of Molecular Biology in 2020.Synthetic Route of C16H10O7 The following contents are mentioned in the article:
The self-assembly of the 42-residue amyloid-β peptide, Aβ42, into fibrillar aggregates is associated with neuronal dysfunction and toxicity in Alzheimer’s disease (AD) patient brains, suggesting that small mols. acting on this process might interfere with pathogenesis. Here, we present exptl. evidence that the small mol. sclerotiorin (SCL), a natural product belonging to the group of azaphilones, potently delays both seeded and nonseeded Aβ42 polymerization in cell-free assays. Mechanistic biochem. studies revealed that the inhibitory effect of SCL on fibrillogenesis is caused by its ability to kinetically stabilize small Aβ42 oligomers. These structures exhibit low β-sheet content and do not possess seeding activity, indicating that SCL acts very early in the amyloid formation cascade before the assembly of seeding-competent, β-sheet-rich fibrillar aggregates. Investigations with NMR WaterLOGSY experiments confirmed the association of Aβ42 assemblies with SCL in solution Furthermore, using ion mobility-mass spectrometry, we observed that SCL directly interacts with a small fraction of Aβ42 monomers in the gas phase. In comparison to typical amyloid fibrils, small SCL-stabilized Aβ42 assemblies are inefficiently taken up into mammalian cells and have low toxicity in cell-based assays. Overall, these mechanistic studies support a pathol. role of stable, β-sheet-rich Aβ42 fibrils in AD, while structures with low β-sheet content may be less relevant. This study involved multiple reactions and reactants, such as 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9Synthetic Route of C16H10O7).
1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9) belongs to benzofurans derivatives. Benzofuran derivatives are one of the most important oxygen-containing heterocycles. Introduction of benzofurans in organic synthesis, particularly drug synthesis, involves generally the use of their metalated species as nucleophiles in addition reactions or in metal-catalysed cross-coupling reactions.Synthetic Route of C16H10O7
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem