title: In silico and in vitro characterization of anti-amyloidogenic activity of vitamin K3 analogues for Alzheimer's disease.
abstract: BACKGROUND
  Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 15 synthesized vitamin K3 (VK3) analogues were studied for their anti-amyloidogenic activity.
  
  
  METHODS
  Biological and spectroscopic assays were used to characterize the effect of VK3 analogues on amyloidogenic properties of Aβ, such as aggregation, free radical formation, and cell viability. Molecular dynamics simulation was used to calculate the binding affinity and mode of VK3 analogue binding to Aβ.
  
  
  RESULTS
  Both numerical and experimental results showed that several VK3 analogues, including VK3-6, VK3-8, VK3-9, VK3-10, and VK3-224 could effectively inhibit Aβ aggregation and conformational conversion. The calculated inhibition constants were in the μM range for VK3-10, VK3-6, and VK3-9 which was similar to the IC50 of curcumin. Cell viability assays indicated that VK3-9 could effectively reduce free radicals and had a protective effect on cytotoxicity induced by Aβ.
  
  
  CONCLUSIONS
  The results clearly demonstrated that VK3 analogues could effectively inhibit Aβ aggregation and protect cells against Aβ induced toxicity. Modified VK3 analogues can possibly be developed as effective anti-amyloidogenic drugs for the treatment of AD.
  
  
  CONCLUSIONS
  VK3 analogues effectively inhibit Aβ aggregation and are highly potent as anti-amyloidogenic drugs for therapeutic treatment of AD.
authors.affiliation: Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Viet Nam.
authors.forename: Pham Dinh Quoc
authors.initials: PD
authors.lastname: Huy
authors.forename: Yao-Chung
authors.initials: YC
authors.lastname: Yu
authors.forename: Son Tung
authors.initials: ST
authors.lastname: Ngo
authors.forename: Tran Van
authors.initials: TV
authors.lastname: Thao
authors.forename: Chin-Piao
authors.initials: CP
authors.lastname: Chen
authors.forename: Mai Suan
authors.initials: MS
authors.lastname: Li
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D024483:Vitamin K 3 / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D005609:Free Radicals; D024483:Vitamin K 3