Palladium (II)-N-heterocyclic Carbene Complexes: Synthesis, molecular Docking, UV-Vis Absorption and enzyme inhibition

Alzheimer's disease is the most prevalent form of dementia; it affects the brain regions responsible for thought, memory, and language. Dementia cannot currently be cured by any medication. We aimed to synthesize Pd-NHC type PEPPSI and investigate their biological activity in anticholinesterase enzymes. In this study, we described preparing a series of Pd-NHC type PEPPSI obtained from their unsymmetrical benzimidazolium salts. These complexes (3a-f) were synthesized from the 2-chloromethyl-1,3-dioxalane benzimidazolium salts, PdCl2, KBr and pyridine. The compounds (3a-f) were tested against two enzymes (AChE and BChE). The results showed that most of the Palladium–NHC complexes effectively inhibited AChE with IC50 values in the range of 4.94 - 40.03 μM, and for BChE are in the range of 4.21 - 21.28 μM. The results showed that the compound (3a) was the most potent inhibitor activity against both AChE and BChE. The inhibition parameter (IC50) was calculated by the spectrophotometric method. The inhibitory effects of the synthesized Pd-NHCs were compared to galantamine as a clinical cholinergic enzyme inhibitor. Additionally, Molecular docking is carried out to estimate the binding pattern between the newly synthesized compounds and both AChE and BChE active sites. The results demonstrated that all synthesized compounds show excellent to moderate inhibition against the examined enzymes (AChE/BChE).