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  2. Synthesis, biological evaluation, theoretical calculations, QSAR and molecular docking studies of novel arylaminonaphthols as potent antioxidants and BChE inhibitors

Synthesis, biological evaluation, theoretical calculations, QSAR and molecular docking studies of novel arylaminonaphthols as potent antioxidants and BChE inhibitors

  • Bioorg Chem. 2024 Sep:150:107598. doi: 10.1016/j.bioorg.2024.107598.
Racha Amira Benoune 1 Mohamed Abdesselem Dems 2 Raouf Boulcina 3 Chawki Bensouici 2 Anthony Robert 4 Dominique Harakat 4 Abdelmadjid Debache 1
Affiliations

Affiliations

  • 1 Laboratory of Synthesis of Molecules with Biological Interest, Faculty of Exact Sciences, Mentouri - Constantine 1 University, 25000 Constantine, Algeria.
  • 2 Biotechnology Research Center,25000 Constantine, Algeria.
  • 3 Laboratory of Synthesis of Molecules with Biological Interest, Faculty of Exact Sciences, Mentouri - Constantine 1 University, 25000 Constantine, Algeria; Department of Engineering Process, Faculty of Technology, Mostefa Benboulaïd-Batna 2 University, 5000 Batna, Algeria. Electronic address: r.boulcina@univ-batna2.dz.
  • 4 Reims Champagne-Ardenne University, CNRS UMR 7312, ICMR, URCATech, 51100 Reims, France.
Abstract

A completely green protocol was developed for the synthesis of a series of arylaminonaphthol derivatives in the presence of N-ethylethanolamine (NEEA) as a catalyst under ultrasonic irradiation and solventless conditions. The major assets of this methodology were the use of non-toxic organic medium, available catalyst, mild reaction condition, and good to excellent yield of desired products. All of the synthesized products were screened for their in vitro antioxidant activity using DPPH, ABTS, and Ferric-phenanthroline assays and it was found that most of them are potent antioxidant agents. Also, their butyrylcholinesterase inhibitory activity has been investigated in vitro. All tested compounds exhibited potential inhibitory activity toward BuChE when compared to standard reference drug galantamine, however, compounds 4r, 4u, 4 g and 4x gave higher butyrylcholinesterase inhibitory with IC50 values of 14.78 ± 0.65 µM, 16.18 ± 0.50 µM, 20.00 ± 0.50 µM, and 20.28 ± 0.08 µM respectively. On the other hand, we employed density functional theory (DFT), calculations to analyze molecular geometry and global reactivity descriptors, and MESP analysis to predict electrophilic and nucleophilic attacks. A quantitative structure-activity relationship (QSAR) investigation was conducted on the antioxidant and butyrylcholinesterase properties of 25 arylaminonaphthol derivatives, resulting in robust and satisfactory models. To evaluate their anti-Alzheimer's activity, compounds 4 g, 4q, 4r, 4u, and 4x underwent docking simulations at the active site of the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), revealing why these compounds displayed superior activity, consistent with the biological findings.

Keywords

Antioxidant agents; Arylaminonaphthols; BChE inhibitors Theoretical calculations; Molecular docking; QSAR.

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