In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes

Abstract

Aim: To investigate the binding mode of synthesized adamantly derivatives inside of cholinesterase enzymes using molecular docking simulations. Methods: A series of hybrid compounds containing adamantane and hydrazide moieties was designed and synthesized. Their inhibitory activities against acetylcholinesterase (AChE) and (butyrylcholinesterase) BChE were assessed in vitro. The binding mode of the compounds inside cholinesterase enzymes was investigated using Surflex-Dock package of Sybyl7.3 software. Results: A total of 26 adamantyl derivatives were synthesized. Among them, adamantane-1-carboxylic acid hydrazide had an almost equal inhibitory activity towards both enzymes, whereas 10 other compounds exhibited moderate inhibitory activity against BChE. The molecular docking studies demonstrated that hydrophobic interactions between the compounds and their surrounding residues in the active site played predominant roles, while hydrophilic interactions were also found. When the compounds were docked inside each enzyme, they exhibited stronger interactions with BChE over AChE, possibly due to the larger active site of BChE. The binding affinities of the compounds for BChE and AChE estimated were in agreement with the experimental data. Conclusion:The new adamantly derivatives selectively inhibit BChE with respect to AChE, thus making them good candidates for testing the hypothesis that BChE inhibitors would be more efficient and better tolerated than AChE inhibitors in the treatment of Alzheimer's disease.

Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment

“…As in many other cases, these differences between the active site gorge structures in AChE and BChE dictate the selective inhibition of these related enzymes5354. It is noteworthy that selective inhibition of BChE compared with AChE was also found for adamantyl derivatives known from the literature5556.…”

Synthesis, Characterization, Crystal Structure, and DFT Study of a New Square Planar Cu(II) Complex Containing Bulky Adamantane Ligand

“…The ligand was prepared as described [ 30 , 31 ] by refluxing an equimolar mixture of admantane-1-carboxylic acid hydrazine with furane-2-caebaldehyde in ethanol to produce the desired ligand, which was identified with an authentic sample [ 30 , 31 ]. The reaction of L with copper(II) bromide (CuBr 2 ) under the solvothermal condition results in the formation of Cu(II) complex ( Scheme 1 ).…”

“…The copper(II) complex of N′ -(furan-2-ylmethylene)adamantne-1-carbohydrazide ligand (L) was prepared by the addition of a hot ethanol solution of the previously reported ligand (L) by our group [ 30 , 31 ] to an equimolar amount of copper(II) bromide [ 38 ]. The complex was precipitated immediately during stirring of the reaction mixture on a magnetic stirrer at room temperature.…”

“…It is still a challenging task to collect active functional groups in a compound, especially for drugs [ 29 ]. Quite recently, we reported the synthesis of new adamantane-containing hydrazone compounds, where furan was one of the arms within the hydrazine-adamantyl compounds [ 30 , 31 ]. Herein, we report on the synthesis and study of the structural properties of copper(II) complex of N′ -(furan-2-ylmethylene)adamantne-1-carbohydrazide which may possess a potent anticancer activity.…”

Design, Synthesis and Characterization of Novel Isoxazole Tagged Indole Hybrid Compounds

“…All reactions were monitored by thin layer chromatography (TLC) using Merck aluminum plates pre-coated with silica gel PF254; 20 × 20 × 0.25 mm, and detected by visualization of the plate under UV lamp (λ = 254 or 365 nm ). Spots were also detected by spraying with anisaldehyde-sulphuric acid in ethanol, followed by heating to 140°C [35].…”