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New benzamide derivatives and their nicotinamide/cinnamamide analogs as cholinesterase inhibitors

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Abstract

In this study, a total of 18 new benzamide/ nicotinamide/ cinnamamide derivative compounds were designed and synthesized for the first time (except B1 and B5) by conventional and microwave irradiation methods. The chemical structures of the synthesized compounds were characterized by 1H NMR, 13C NMR, and HRMS spectra. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition effects of the compounds were evaluated to find out new possible drug candidate molecule/s. According to the inhibition results, the IC50 values of the compounds synthesized were in the range of 10.66–83.03 nM towards AChE, while they were in the range of 32.74–66.68 nM towards BuChE. Tacrine was used as the reference drug and its IC50 values were 20.85 nM and 15.66 nM towards AChE and BuChE, respectively. The most active compounds B4 (IC50: 15.42 nM), N4 (IC50: 12.14 nM), and C4 (IC50: 10.67 nM) in each series towards AChE were docked at the binding site of AChE enzyme to explain the inhibitory activities of each series. On the other hand, the compounds B4, N4, and C4 showed satisfactory pharmacokinetic properties via the prediction of ADME profiles.

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Acknowledgements

I would like to thank Prof. Dr. Hasan Seçen for supporting this study with laboratory facilities, knowledge, and experience.

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  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, TR-25240, Erzurum, Turkey

    Mehmet Koca & Sinan Bilginer

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Koca, M., Bilginer, S. New benzamide derivatives and their nicotinamide/cinnamamide analogs as cholinesterase inhibitors. Mol Divers 26, 1201–1212 (2022). https://doi.org/10.1007/s11030-021-10249-9

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