Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer’s disease treatment

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• 作者：Lukas Hroch^a ; ^b ; Patrick Guest^c ; Ondrej Benek^b ; ^d ; Ondrej Soukup^b ; Jana Janockova^b ; Rafael Dolezal^b ; ^d ; ^e ; Kamil Kuca^b ; ^d ; Laura Aitken^c ; Terry K. Smith^c ; Frank Gunn-Moore^c ; Dominykas Zala^c ; Rona R. Ramsay^c ; ; Kamil Musilek^b ; ^d ; ^{kamil.musilek@gmail.com}
• 关键词：Alzheimer's disease (AD) ; Monoamine oxidase (MAO) ; Amyloid-beta peptide (Aβ) ; Mitochondrial amyloid-binding alcohol dehydrogenase (ABAD) ; 17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) ; Horseradish peroxidase (HRP)
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：25
• 期：3
• 页码：1143-1152
• 全文大小：1877 K
• 卷排序：25

文摘

Novel frentizole-based indolyl thiourea analogues were prepared as potential MAO/ABAD inhibitors. Compound 19 displayed low micromolar and high nanomolar IC50 value for MAO-A and MAO-B inhibition. Compounds 17 and 21 showed important structural features for future design of ABAD inhibitors. Several reported compounds acted as low micromolar HRP inhibitors. The active compounds demonstrated low cytotoxicity profile.