Regioselective pyrrolizidine bis-spirooxindoles as efficient anti-amyloidogenic agents

Nilamuni H de Silva; Anthony Dahdah; Ewan W Blanch; Helmut M Hügel; Subashani Maniam

doi:10.1016/j.ejmech.2022.114566

Regioselective pyrrolizidine bis-spirooxindoles as efficient anti-amyloidogenic agents

Eur J Med Chem. 2022 Oct 5:240:114566. doi: 10.1016/j.ejmech.2022.114566. Epub 2022 Jun 26.

Authors

Nilamuni H de Silva¹, Anthony Dahdah², Ewan W Blanch², Helmut M Hügel², Subashani Maniam³

Affiliations

¹ School of Science, STEM College, RMIT University, 124 La Trobe Street, Melbourne, VIC, 3001, Australia. Electronic address: nilamuni.desilva@rmit.edu.au.
² School of Science, STEM College, RMIT University, 124 La Trobe Street, Melbourne, VIC, 3001, Australia.
³ School of Science, STEM College, RMIT University, 124 La Trobe Street, Melbourne, VIC, 3001, Australia. Electronic address: subashani.maniam@rmit.edu.au.

PMID: 35785723
DOI: 10.1016/j.ejmech.2022.114566

Abstract

Here, we report a microwave-assisted, one-pot, three-component, 1,3-dipolar cycloaddition reaction to produce highly regioselective and stereoselective bis-spirooxindoles as potential inhibitors against amyloid-β fibrillation. Ease of synthesis, promising anti-amyloidogenic activity, low toxicity, and in vitro blood brain barrier permeability makes these compounds attractive therapeutic leads to treat Alzheimer's disease.

Keywords: Alzheimer's disease; Amyloid-β; Protein misfolding; Raman spectroscopy; Spirooxindole.

MeSH terms

Alzheimer Disease* / drug therapy
Amyloid beta-Peptides*
Blood-Brain Barrier
Cycloaddition Reaction
Humans

Substances

Amyloid beta-Peptides