Synthesis and Cholinesterase Inhibitory Potentials of (5-formylfuran-2-yl) methyl 3,4-dimethoxy/nitro benzoates

Year 2022, Volume: 12 Issue: 3, 1345 - 1357, 01.09.2022

Mehmet Koca

https://doi.org/10.21597/jist.1117484

Abstract

Cholinesterase (ChE) inhibitors are an important group of drugs used in Alzheimer's, glaucoma, and myasthenia gravis. In recent years, cholinesterase inhibition potentials of compounds have been investigated in new drug discovery studies. In this study (5-formylfuran-2-yl) methyl 4-nitro benzoate (compound 1) and newly designed (5-formylfuran-2-yl) methyl 3,4-dimethoxybenzoate (compound 2) were synthesized. The chemical structures of the synthesized compounds were characterized by spectral data (HRMS, 1H NMR, and 13C NMR). The ChE inhibitory activity of the compounds was evaluated using in vitro colorimetric Ellman method. Compound 1 and compound 2 exhibited inhibitory activity against AChE at IC50 values of 3.25 μM and 8.45 μM, respectively. Compound 1 and Compound 2 showed inhibitory activity against BuChE at IC50 values of 8.45 μM and 14.44 μM, respectively. In Docking simulations with 1EVE and 1P0I, the binding free energy scores of compound 1 were higher than the binding free energy scores of compound 2. In this respect, in silico molecular docking studies overlapped with in vitro enzyme inhibition studies. These derivatives can be used to develop new drugs such as cholinesterase inhibitors.

Keywords

Benzoate, cholinesterase, inhibition, molecular docking, synthesis

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