PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) continues to be a worldwide health concern, demanding innovative therapeutic approaches. This study investigates the neuroprotective potential of herbal compounds by scrutinizing their interactions with Beta-Secretase-1 (BACE1). Through comprehensive molecular docking analyses, three compounds, Masticadienonic acid (ΔG: -9.6 kcal/mol), Hederagenin (ΔG: -9.3 kcal/mol), and Anthocyanins (ΔG: -8.1 kcal/mol), emerge as promising BACE1 ligands, displaying low binding energies and strong affinities. ADME parameter predictions, drug-likeness assessments, and toxicity analyses reveal favorable pharmacokinetic profiles for these compounds. Notably, Masticadienonic Acid exhibits optimal drug-likeness (-3.3736) and negligible toxicity concerns. Hederagenin (drug-likeness: -5.3272) and Anthocyanins (drug-likeness: -6.2041) also demonstrate promising safety profiles. Furthermore, pharmacophore modeling elucidates the compounds\' unique interaction landscapes within BACE1\'s active site. Masticadienonic acid showcases seven hydrophobic interactions and a hydrogen bond acceptor interaction with Thr232. Hederagenin exhibits a specific hydrogen bond acceptor interaction with Trp76, emphasizing its selective binding. Anthocyanins reveal a multifaceted engagement, combining hydrophobic contacts and hydrogen bond interactions with key residues. In conclusion, Masticadienonic acid, Hederagenin, and Anthocyanins stand out as promising candidates for further experimental validation, presenting a synergistic balance of efficacy and safety in combating AD through BACE1 inhibition.
摘要：
阿尔茨海默病（AD）仍然是一个世界性的健康问题，要求创新的治疗方法。这项研究通过仔细检查它们与β-分泌酶-1（BACE1）的相互作用来调查草药化合物的神经保护潜力。通过全面的分子对接分析，三种化合物,乳房二烯酸（ΔG：-9.6kcal/mol），Hederagenin（ΔG：-9.3kcal/mol），和花色苷（ΔG：-8.1kcal/mol），作为有前途的BACE1配体出现，显示低结合能和强亲和力。ADME参数预测，药物相似性评估，和毒性分析揭示了这些化合物的有利药代动力学特征。值得注意的是,MasticadienonicAcid表现出最佳的药物相似度（-3.3736）和可忽略的毒性问题。Hederagenin（药物相似度：-5.3272）和花青素（药物相似度：-6.2041）也显示出有希望的安全性。此外，药效基团建模阐明了化合物在BACE1活性位点内的独特相互作用景观。Masticadienonicacid展示了七个疏水相互作用和与Thr232的氢键受体相互作用。Hederagenin表现出与Trp76的特异性氢键受体相互作用，强调了其选择性结合。花青素揭示了多方面的参与，结合疏水接触和氢键与关键残基的相互作用。总之,乳房二烯酸，Hederagenin,花青素作为进一步实验验证的有希望的候选者，在通过BACE1抑制对抗AD中呈现功效和安全性的协同平衡。
