7-hydroxyflavone and Neuroblastoma

A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-β (Aβ₁₋₄₂) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Aβ₁₋₄₂ aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Chelating Agents; Cholinesterase Inhibitors; Cholinesterases; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Flavonoids; Free Radical Scavengers; Humans; Mice; Neuroblastoma; Organometallic Compounds; Oxidation-Reduction; Peptide Fragments; Picrates; Structure-Activity Relationship; Tacrine