Sakayanathan_2019_Int.J.Biol.Macromol_140_1147

In Alzheimer's disease (AD) and diabetes-associated cognitive decline, the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity is increased. AChE exists as different globular molecular forms: tetramer (G4), dimer (G2) and monomer (G1). In adult brain, G4 form is abundant however in AD, the ratio of lower molecular forms (G1) to G4 form increased. Hence, the present study delineated the inhibition of novel astaxanthin-s-allyl cysteine (AST-SAC) against BChE and various molecular forms of AChE. Cobra venom, human erythrocyte and Electrophorus electricus was used as source of G1, G2 and G4 form of AChE. AST-SAC showed inhibition against G1 (IC50=0.72muM, competitive, Ki=0.66muM), G2 (IC50=0.65muM, mixed, Ki=0.50muM) and G4 (IC50=0.67muM, competitive, Ki=0.67muM) form of AChE. AST-SAC inhibited human brain AChE (IC50=0.84muM, competitive, Ki=0.53muM) and human serum BChE (IC50=0.80muM, competitive, Ki=0.58muM). In silico analysis revealed the interaction of AST-SAC with the amino acids present in peripheral anionic and catalytic site of human AChE and BChE. Molecular dynamics simulation confirmed the stable interaction of AST-SAC in the active site gorge of AChE and BChE.