Synthesis of Denosomin–Vitamin D₃ Hybrids and Evaluation of Their Anti-Alzheimer’s Disease Activities

As an extension of previously conducted studies on developing an anti-Alzheimer’s disease agent, denosomin (1-deoxy-24-norsominone, an artificial inducer of neurite elongation), derivatives were designed and synthesized based on the hypothesis that our denosomin would exhibit axonal extension activity via a 1,25D₃-membrane-associated, rapid response steroid-binding protein (1,25D₃-MARRS) pathway. The biological assay revealed that the hybridization of characteristic δ-lactone in denosomin and the triene moiety in VD₃ was effective to enhance the nerve re-extension activity in amyloid β (Aβ)-damaged neurons.