Title Inhibitory effects of fluorinated benzenesulfonamides on insulin fibrillation /
Authors Hadi Ali Janvand, Saeid ; Ladefoged, Lucy Kate ; Zubrienė, Asta ; Sakalauskas, Andrius ; Christiansen, Gunna ; Dudutienė, Virginija ; Schiøtt, Birgit ; Matulis, Daumantas ; Smirnovas, Vytautas ; Otzen, Daniel E
DOI 10.1016/j.ijbiomac.2022.12.105
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Is Part of International journal of biological macromolecules.. Amsterdam : Elsevier. 2023, vol. 227, p. 590-600.. ISSN 0141-8130. eISSN 1879-0003
Keywords [eng] carbonic anhydrase inhibitors ; insulin ; protein fibrillation inhibitors ; sulfonamide compounds
Abstract [eng] 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.
Published Amsterdam : Elsevier
Type Journal article
Language English
Publication date 2023
CC license CC license description