Multitarget drug design strategy against Alzheimer's disease: Homoisoflavonoid Mannich base derivatives serve as acetylcholinesterase and monoamine oxidase B dual inhibitors with multifunctional properties.

A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC ₅₀ =2.49±0.08nM and 1.74±0.0581μM, respectively), good self- and Cu ²⁺ -induced Aβ _1-42 aggregation inhibitory potency, antioxidant activity, biometal chelating ability and high BBB permeability. These multifunctional properties make 10d as an excellent candidate for the development of efficient drugs against AD.
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