Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Derivatives and Their Neuroprotective Activities

Twenty natural -product -like 2,8-dioxabicyclo[3.3.1]nonane derivatives were synthesized and their neuroprotective activities were tested using human monoamine oxidases (MAO) A and B and acetyl and butyryl cholinesterases (ChE). Compound 1s showed inhibitory activity for MAO -A, MAO -B and acetylcholinesterase (AChE) (IC50 values 34.0, 2.3 and 11.0 mu M, respectively). The inhibition mode of (-)-1s for MAO -B was investigated. Chiral HPLC of (+/-)-1s separated the enantiomers and (-)-1s showed MAO -B inhibitory activity. Molecular docking simulation of (-)-1s and MAO -B revealed the binding mode.