title: Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.
abstract: There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.
authors.affiliation: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. snab@ukm.edu.my.
authors.forename: Syed Nasir Abbas
authors.initials: SN
authors.lastname: Bukhari
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Jantan
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D066329:Protein Aggregates / Q000187:drug effects; D066263:Protein Aggregation, Pathological / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D066329:Protein Aggregates; D003474:Curcumin