Organofluorine Inhibitors of Amyloid Fibrillogenesis
| العنوان: | Organofluorine Inhibitors of Amyloid Fibrillogenesis |
|---|---|
| المؤلفون: | Mohammed Abid, Shilpa C. Mhadgut, Béla Török, Marianna Török |
| المصدر: | Biochemistry. 45:5377-5383 |
| بيانات النشر: | American Chemical Society (ACS), 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Indole test, chemistry.chemical_classification, Amyloid beta-Peptides, Trifluoromethyl, Molecular Structure, Amyloid, Chemistry, Stereochemistry, Carboxylic acid, Fluorine Compounds, Fibrillogenesis, Biochemistry, Structure-Activity Relationship, chemistry.chemical_compound, Microscopy, Electron, Transmission, Drug Design, Molecule, IC50, Stoichiometry |
| الوصف: | The design and application of an effective, new class of organofluorine inhibitors of amyloid fibrillogenesis are described. Based on experimental evidence a core structure containing indol-3-yl, trifluoromethyl, hydroxyl, and carboxylic acid ester functions has been designed. Several substituted derivatives of this core structure have been synthesized, using various indole derivatives. While all inhibitor candidates have shown considerable effect (20-70% inhibition) in structure-activity relationship studies (inhibitor/Abeta = 10 ratio), several compounds have demonstrated excellent activity (93-96% inhibition). Using concentration dependence studies, the activity of the most active molecules have been quantified. These inhibitors practically completely block the fibril formation of Abeta(1)(-)(40), as shown by maximum inhibition values (IC(max) = 98-100%). The median inhibitor concentration values (IC(50) = 0.23-0.53 mol(inhibitor)/mol(A)(beta)) demonstrate favorable stoichiometry for the inhibition. The respective elimination of the functional groups from the core structure has resulted in a partial or complete loss of activity, indicating the significant role of each group. Experiments with these derivatives suggest the particular importance of the acidic hydroxyl group during peptide-inhibitor interaction. |
| تدمد: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi0601104 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4388a94250adf609727cfc149c2cd46 https://doi.org/10.1021/bi0601104 |
| رقم الانضمام: | edsair.doi.dedup.....a4388a94250adf609727cfc149c2cd46 |
| قاعدة البيانات: | OpenAIRE |
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