Degradation of amyloid peptide aggregates by targeted singlet oxygen delivery from a benzothiazole functionalized naphthalene endoperoxide

Aggregate structures formed by amyloid-beta (A beta) are correlated with the progression of pathogenesis in Alzheimer's disease. Previous works have shown that photodynamic photosensitizers were effective in oxidatively degrading amyloid-beta aggregates and thus decreasing their cytotoxicity under various conditions. In this work, we designed and synthesized a benzothiazole-naphthalene conjugate, with high level of structural analogy to Thioflavin T which is known to have high affinities for the amyloid peptide aggregates. The endoperoxide form (BZTN-O-2) of this compound, which releases singlet oxygen with a half-life of 77 minutes at 37 degrees C, successfully inhibited and/or reversed amyloid aggregation. The endoperoxide is capable of singlet oxygen release without any need for light, and its charge-neutral form could allow blood-brain barrier (BBB) permeability. The therapeutic potential of such endoperoxide compounds with amyloid binding affinity is exciting.

Automated summary

A newly discovered compound shows potential in inhibiting and reversing the pathogenesis of Alzheimer's disease. It releases singlet oxygen, reducing the cytotoxicity of amyloid-beta aggregates, and has good blood-brain barrier permeability.