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Such adducts hamper the aggregation and deposition of fibrils. A novel reaction of <jats:bold>BA<\/jats:bold> with pentylamine (<jats:bold>PA<\/jats:bold>) as a model for the lysine side chain is described. This is the first study addressing the atomistic details of a Schiff base reaction with the trihydroxylated moiety of <jats:bold>BA<\/jats:bold>. Nuclear magnetic resonance and mass spectrometry approaches clearly indicate the formation of dehydrobaicalein in solution as well as its condensation with <jats:bold>PA<\/jats:bold> under aerobic conditions, yielding regioselectively C6\u2010substituted products. The combined results suggest initial ion pair formation between <jats:bold>BA<\/jats:bold> and <jats:bold>PA<\/jats:bold>, followed by a redox chain reaction: the initiation by oxygen\/air; an <jats:italic>o<\/jats:italic>\u2010quinone\u2010based chain involving oxidation and reduction steps; and extra off\u2010chain formation of a doubly oxidized product. These mechanistic details support the anti\u2010amyloid activity of <jats:bold>BA<\/jats:bold> and endorse its trihydroxyphenyl moiety as a pharmacophore for drug\u2010design studies.<\/jats:p>","DOI":"10.1002\/chem.202104240","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T07:04:07Z","timestamp":1641452647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Combined in Silico and in Vitro Approaches To Uncover the Oxidation and Schiff Base Reaction of Baicalein as an Inhibitor of Amyloid Protein Aggregation"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3130-9807","authenticated-orcid":false,"given":"Nat\u00e9rcia F.","family":"Br\u00e1s","sequence":"first","affiliation":[{"name":"LAQV, REQUIMTE Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias Universidade do Porto  Rua do Campo Alegre s\/n 4169-007 Porto 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