Anti-arrhythmic Medication Propafenone a Potential Drug for Alzheimer's Disease Inhibiting Aggregation of Aβ: In Silico and in Vitro Studies.
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.
Institute for Computational Science and Technology , Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.|Institute of Physics, Polish Academy of Sciences , Al. Lotnikow 32/46, 02-668 Warsaw, Poland.
Son Tung
ST
Ngo
Shang-Ting
ST
Fang
Shu-Hsiang
SH
Huang
Department of Neurology, Mackay Memorial Hospital , New Taipei City, 252 Taiwan.
Chao-Liang
CL
Chou
Institute for Computational Science and Technology , Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.|Institute of Physics, Polish Academy of Sciences , Al. Lotnikow 32/46, 02-668 Warsaw, Poland.
Pham Dinh Quoc
PD
Huy
Institute of Physics, Polish Academy of Sciences , Al. Lotnikow 32/46, 02-668 Warsaw, Poland.
Mai Suan
MS
Li
Yi-Cheng
YC
Chen
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000889:Anti-Arrhythmia Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D003474:Curcumin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005609:Free Radicals / Q000378:metabolism; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011405:Propafenone / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D066329:Protein Aggregates / Q000187:drug effects*; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics
D016229:Amyloid beta-Peptides; D000889:Anti-Arrhythmia Agents; D005609:Free Radicals; D010446:Peptide Fragments; D066329:Protein Aggregates; C078592:amyloid beta-protein (1-40); D011405:Propafenone; D003474:Curcumin