A new guanylhydrazone derivative as a potential acetylcholinesterase inhibitor for Alzheimer's disease: synthesis, molecular docking, biological evaluation and kinetic studies by nuclear magnetic resonance

Abstract

Molecular docking, in silico studies and NMR show that the new guanylhydrazone is a promising compound for the treatment of Alzheimer's disease.

Synthesis of New Quinoline-Piperonal Hybrids as Potential Drugs against Alzheimer’s Disease

“…According Sugimoto et al [30], carbonyl groups conjugated to aromatic rings are important for inhibition of AChE. However, Ferreira Neto et al [25] showed that the presence of a guanyl-hydrazone allows interactions with the catalytic anionic site (CAS) of AChE, improving the activity, as also shown here.…”

“…NMR is a good method for the biological evaluation of AChE inhibitors. Recent published works have indicated results consistent with Ellman’s method [25,32,33,34,35,36]. In our study we used the NMR method [29] to determine the concentrations of the substrate (ACh) and the product acetate (Ac), which are obtained from direct integration of the corresponding absorption peaks for methyl groups (2.24 ppm for ACh and 2.16 ppm for Ac) [32,35].…”

“…The inhibitory activities of compounds (3) – (8) were evaluated through the modified spectrophotometric Ellman’s method [25,26] on Ee AChE and butyrylcholinesterase from equine serum (EqBChE). Results (Table 2) show that while compound (4) is not able to inhibit any of the enzymes, compound (8) is a non-selective inhibitor of both enzymes, being twice more potent in inhibiting Ee AChE (IC 50 = 8.50 ± 0.39 μM ) than EqBChE (IC 50 = 15.16 ± 0.75 μM).…”

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

“…The choice of the TcAChE instead of an Electrophorus electricus model of AChE (which was employed for the Ellman assay) was based on the good resolution of the structure (2.5 Å), the similarity of the ligand in the structure with compound 4 and the unavailability of high resolution EeAChE structures. 47 It is worth noting the high degree of identity between TcAChE and EeAChE. 48 Water molecules and the original ligand were removed from the protein structure and polar hydrogens and charges were added.…”

Synthesis, Biological Evaluation and Docking Studies of Chalcone and Flavone Analogs as Antioxidants and Acetylcholinesterase Inhibitors

“…A small turn of the nitro or hydroxyl groups would be needed for this to happen, but a weak interaction between them might be helping the interaction of 2d with this residue. The clearer interactions for 2d appear with Trp84, a residue that has been reported as an important one for ligand interactions (especially with quaternary groups from acetylcholine and other compounds) [58,62]. In this case, Trp84 is near the positively charged nitrogen of the nitro group, although its position appears to be almost over the B ring of the chalcone, allowing for π-π stacking at 3.7 Å.…”