Investigation of the acetylcholinesterase and butyrylcholinesterase inhibitory activities of water-soluble phthalocyanine compounds

Neurodegenerative diseases are defined as progressive diseases of the central nervous system (CNS). Alzheimer's disease (AD) is the most common type of disease in this group. The aforementioned patients manifest symptoms of dementia, cognitive impairment, and personality changes. At present, therapeutic interventions are confined to the administration of symptomatic therapies, with no efficacious strategies available to retard the progression of the disease. Consequently, there is an urgent need to identify new therapeutic targets associated with the pathogenesis of the disease. In this study, phthalocyanine derivatives were screened in silico against AChE (Acetylcholinesterase) and BuChE (butyrylcholinesterase) enzymes using a molecular docking method. The binding energy values obtained were found to be of considerable significance, indicating an interaction with amino acids in the active sites of the enzymes. This suggests the potential for competitive inhibition. The compound 3PY.H2O demonstrated strong binding affinities of -8.5 kcal/mol with AChE and -10.7 kcal/mol with BuChE. The enzyme inhibition potential of the compounds was evaluated, and the IC50 values for AChE were found to be 6.17 ± 1.73, 8.67 ± 0.97, and 8.61 ± 0.88 µM for 3PY.H2O, 3PY.NiQ, and 3PY.CoQ, respectively. The results of the kinetic studies demonstrated that all three phthalocyanines exhibited competitive inhibition, with the 3PY.NiQ compound exhibiting the most effective competitive inhibitor activity. The inhibitor activities of the compounds were observed to be 3PY.NiQ > 3PY.CoQ > 3PY.H2O. No significant DNA damage was observed in the electroforetically examined DNA hydrolysis, oxidative, and photonuclease activities of the compounds. The findings suggest that the phthalocyanine derivatives previously referenced may have potential as drug candidates for the treatment of Alzheimer's disease. This finding offers a strong possibility for subsequent validation methods in both in vivo and in vitro contexts.