Acetylcholinesterase (AChE) and paraoxonase 1 (PON1) are two important serum ester hydrolases that have antiatherosclerotic effect by inhibiting the oxidation of lipid peroxides. In addition, AChE inhibitors are target molecules for the treatment of Alzheimer's. Naphthalene derivatives are important molecules in the field of pharmacology due to their wide range of biological activities. In this study, the inhibition effects of naphthalenylmethylen hydrazine derivatives on these two metabolic enzymes were investigated. IC 50 values of these molecules were determined in the range of 0.158 μM to 6.862 μM against PON1, 0.0214 μM to 0.675 μM against AChE. As a result, naphthalenylmethylen hydrazine derivatives had strong inhibition effect on both enzymes. In this context, we hope that the results obtained in this study contribute to the determination of the side effects of current and new naphthalene-based pharmacological compounds to be developed. And also be effective in the synthesis studies of new AChE inhibitors.
The aim of this study is to purify carbonic anhydrase I and II isoenzymes from human erythrocyte, isolate two natural products osajin (OSJ) and pomiferin (PMF) from Maclura pomifera fruits, and evaluate the in vitro effect of these natural metabolites on these isoenzymes. These natural products may be used as starting points for drug discovery (like drugs used in several therapeutic applications, including antiglaucoma activity). For the purification procedure, the Sepharose-4B-l-tyrosine-sulphonamide affinity chromatography was used. Column chromatography and thin layer chromatography methods were used for isolation of OSJ and PMF from M. pomifera fruits and their chemical structures were elucidated by IR, 1D, and 2D NMR methods. We compared inhibitory effects of these natural products with inhibitory effects of phenolic compounds and found that these products demonstrated average inhibition effects. We thought that this study will give inspiration to scientists interested in this issue.
In this study, a series of N‐substituted‐(p‐tolyl)pyridazin‐3(2H)‐one derivatives were synthesized and evaluated for their AChE inhibitory activity. The chemical structures of novel compounds 5(a–m) were confirmed by 1H‐NMR, 13C‐NMR, IR and HRMS analysis. In order to eliminate the symptomatic effects of Alzheimer's disease, the proposed compounds were evaluated by acetylcholinesterase inhibition activity study in accordance with the cholinergic hypothesis. The results revealed that the N‐substituted‐(p‐tolyl)pyridazin‐3(2H)‐one derivatives inhibited the enzymes significantly. Ki values for acetylcholinesterase in the range of 0.56±0.15–4.12±1.42 μM. Compound 5 h demonstrated the greatest in AChE activity compared with tacrine (0.56±0.15 μM). Molecular docking studies were performed for all compounds that compared tacrine in AChE activity in‐vitro. As a result of molecular docking studies (ΔGBind, docking score, XP Gscore, Glide energy, Glide emodel), 5 f, 5 g and 5 h compounds showed good inhibitory properties in the AChE active site as in silico.
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