Anti-arrhythmic Medication Propafenone a Potential Drug for Alzheimer’s Disease Inhibiting Aggregation of Aβ: In Silico and in Vitro Studies

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• 作者：Son Tung Ngo ; Shang-Ting Fang ; Shu-Hsiang Huang ; Chao-Liang Chou ; Pham Dinh Quoc Huy ; Mai Suan Li ; Yi-Cheng Chen
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2016
• 出版时间：July 25, 2016
• 年：2016
• 卷：56
• 期：7
• 页码：1344-1356
• 全文大小：688K
• 年卷期：0
• ISSN：1549-960X

文摘

Alzheimer’s disease (AD) is the most common form of dementia caused by the formation of Aβ aggregates. So far, no effective medicine for the treatment of AD is available. Many efforts have been made to find effective medicine to cope with AD. Curcumin is a drug candidate for AD, being a potent anti-amyloidogenic compound, but the results of clinical trials for it were either negative or inclusive. In the present study, we took advantages from accumulated knowledge about curcumin and have screened out four compounds that have chemical and structural similarity with curcumin more than 80% from all FDA-approved oral drugs. Using all-atom molecular dynamics simulation and the free energy perturbation method we showed that among predicted compounds anti-arrhythmic medication propafenone shows the best anti-amyloidogenic activity. The in vitro experiment further revealed that it can inhibit Aβ aggregation and protect cells against Aβ induced cytotoxicity to almost the same extent as curcumin. Our results suggest that propafenone may be a potent drug for the treatment of Alzheimer’s disease.