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

作者：Ngo Son Tung; Fang Shang Ting; Huang Shu Hsiang; Chou Chao Liang; Pham Dinh Quoc Huy; Li Mai Suan^*; Chen Yi Cheng^*

来源：Journal of Chemical Information and Modeling, 2016, 56(7): 1344-1356.

DOI：10.1021/acs.jcim.6b00029

Alzheimer's disease (AD) is the most common form of dementia caused by the formation of Afi 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 AO aggregation and protect cells against Afi 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.

• 出版日期2016-7