Development of Pyrimidine‐Substituted Schiff Base and Their Axially Silicon Phthalocyanines as Inhibitors of Acetylcholinesterase and Butyrylcholinesterase for Alzheimer's Disease Therapy

ABSTRACT In this study, axially substituted silicon (IV) phthalocyanine complexes containing pyrimidine‐substituted Schiff bases were synthesized and characterized. The Schiff bases ( Pyr‐1 and Pyr‐2 ) were synthesized through a condensation reaction between pyrimidine derivatives and appropriate aldehydes, followed by their coordination with silicon (IV) to form the corresponding phthalocyanine complexes ( Pyr‐1‐SiPc and Pyr‐2‐SiPc ). The synthesized Schiff bases ( Pyr‐1 and Pyr‐2 ) and silicon (IV) phthalocyanine derivatives ( Pyr‐1‐SiPc and Pyr‐2‐SiPc ) were subsequently tested in vivo for their inhibitory effect on the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). A substantial number of these compounds exhibited pronounced inhibitory activity against both enzymes. Notably, among the phthalocyanines and their precursor compounds, the most intriguing were identified as submicromolar selective inhibitors of AChE and BChE, with IC 50 values of 4.26 μM and 6.46 μM, respectively.