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Inhibitory effects of fluorinated benzenesulfonamides on insulin fibrillation

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  • Saeid Hadi Alijanvand, University of Tehran
  • ,
  • Lucy Kate Ladefoged
  • ,
  • Asta Zubrienė, Vilnius University
  • ,
  • Andrius Sakalauskas, Vilnius University
  • ,
  • Gunna Christiansen, Laboratory for Stem Cell Research Department of Health Science and Technology Aalborg Universitet
  • ,
  • Virginija Dudutiene, Vilnius University
  • ,
  • Birgit Schiøtt
  • Daumantas Matulis, Vilnius University
  • ,
  • Vytautas Smirnovas, Vilnius University
  • ,
  • Daniel E Otzen

Amyloid fibrils are protein aggregates formed by protein assembly through cross β structures. Inhibition of amyloid fibril formation may contribute to therapy against amyloid-related disorders like Parkinson's, Alzheimer's, and type 2 diabetes. Here we report that several fluorinated sulfonamide compounds, previously shown to inhibit human carbonic anhydrase, also inhibit the fibrillation of different proteins. Using a range of spectroscopic, microscopic and chromatographic techniques, we found that the two fluorinated sulfonamide compounds completely inhibit insulin fibrillation over a period of 16 h and moderately suppress α-synuclein and Aβ fibrillation. In addition, these compounds decreased cell toxicity of insulin incubated under fibrillation-inducing conditions. We ascribe these effects to their ability to maintain insulin in the native monomeric state. Molecular dynamic simulations suggest that these compounds inhibit insulin self-association by interacting with residues at the dimer interface. This highlights the general anti-aggregative properties of aromatic sulfonamides and suggests that sulfonamide compounds which inhibit carbonic anhydrase activity may have potential as therapeutic agents against amyloid-related disorders.

Original languageEnglish
JournalInternational Journal of Biological Macromolecules
Volume227
Pages (from-to)590-600
Number of pages11
ISSN0141-8130
DOIs
Publication statusPublished - 2023

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Copyright © 2022. Published by Elsevier B.V.

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