Theoretical evaluation of flavonoids as multipotent agents to combat Alzheimer's disease

As multiple pathogenetic factors, including aggregated amyloid-beta peptide and tau protein, excessive transition metals, oxidative stress and reduced acetylcholine level, have been implicated in Alzheimer's disease (AD), multipotent agents aiming at diverse targets are expected to act better than the single-target-aiming counterparts in the fight against AD. Among the potential multipotent agents, natural products, especially flavonoids (including xanthones), have been given much attention. To explore to what extent the desired multiple pharmacological effects can be combined into one flavonoid molecule, we examined the structural requirements of flavonoids (including xanthones) as inhibitors of monoamine oxidase (including isoenzymes A and B), acetylcholinesterase and/or butyrylcholinesterase. In combination with the known structure-activity relationships of flavonoids as reactive oxygen species scavengers and metal chelators, we provide a theoretical evaluation of flavonoids (including xanthones) as multipotent agents to combat AD, which is of great significance to directing the screening of novel AD-modifying drugs. (c) 2006 Elsevier B.V. All rights reserved.