Curcumin is a natural polyphenol able to bind the amyloid beta peptide, which is related to Alzheimer’s\uddisease, and modify its self-assembly pathway. This paper focuses on a multi-disciplinary study that starts\udfrom the design of curcumin-like compounds with the key chemical features required for inhibiting\udamyloid beta aggregation, and reports the effects of these compounds on the in vitro aggregation of\udamyloid beta peptides. Chemoinformatic screening was performed through the calculation of molecular\uddescriptors that were able to highlight the drug-like profile, followed by docking studies with an amyloid\udbeta peptide fibril. The computational design underlined two different scaffolds that were easily\udsynthesized in good yields. In vitro experiments, ranging from fluorescence spectroscopy and confocal\udmicroscopy up to small angle X-ray scattering, provided evidence that the synthesized compounds are\udable to modify the aggregation pattern of amyloid beta peptides both in the secondary structures, and in\udterms of the overall structure dimensions. The cytotoxic potential of the synthesized compounds was\udfinally tested in vitro with a model neuronal cell line (LAN5). The overall view of this study suggests new\udconcepts and potential difficulties in the design of novel drugs against diverse amyloidoses, including\udAlzheimer’s disease.
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