Development of dual targeting inhibitors against aggregations of amyloid-β and tau protein

• Efficient, one-pot, 3- and 4-component coupling sequences were developed.
• Seventeen structurally diverse, organic functional dyes were rapidly synthesized.
• Two compounds exerted potent anti-aggregating activity against both Aβ and tau.

Aggregations of both amyloid-β (Aβ) and hyper-phosphorylated tau proteins are recognized as key pathological manifestations of Alzheimer's disease (AD). Agents that inhibit both those forms of aggregation show promise as drug candidates. Seventeen oligo heteroaromatic compounds were rapidly synthesized via a one-pot, 3- or 4-component coupling procedure. Evaluations showed that compounds E16 and E18 were the most potent inhibitors of Aβ and tau aggregations (E16: IC50s = 0.38, 0.29 μM against Aβ, tau, respectively, E18: IC50s = 0.55, 0.30 μM against Aβ, tau, respectively).

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