Microwave-assisted rapid synthesis of spirooxindole-pyrrolizidine analogues and their activity as anti-amyloidogenic agents

• Published in: Bioorganic chemistry 2021-09, Vol.114, p.105128-105128, Article 105128
• Main Authors: de Silva, Nilamuni H., Pyreddy, Suneela, Blanch, Ewan W., Hügel, Helmut M., Maniam, Subashani
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid beta; Fluorescence inhibition; Neuroprotection; Protein misfolding; Spicocyclics
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105128

[Display omitted] •Pyrrolizidine nitro spirooxindoles synthesized using cycloaddition reaction.•Microwave-assisted rapid organic synthesis of enantiomerically pure compounds.•Synthesized compounds analysed for their ability to inhibit amyloid-β misfolding.•Fluorescence and Raman spectroscopy with TEM, MTT assay and in silico studies.•Compounds, 4b, 4d and 4e displayed promising amyloid fibril inhibition activity. A library of Sox-pyrrolizidines was rapidly prepared by microwave-assisted, one-pot, three-component, 1,3-dipolar cycloaddition of azomethine ylides from l-proline and isatin, with various β-nitrostyrenes. Nitro-Sox compounds, 4b, 4d and 4e inhibit HEWL amyloid fibril formation by ThT studies with percentages of fluorescence intensity of 55.4, 42.9 and 40.3%, respectively. Further studies with MTT assay, Raman spectroscopy, TEM and molecular docking supported these promising candidates for activity against amyloid misfolding, a phenomenon leading to Alzheimer’s disease pathology.