Abstract: The strategy of the nucleophilic substitution of hydrogen (SNH) was first applied for the metal-free C-H/C-H coupling reactions of 4H-imidazole 3-oxides with indoles. As a result, a series of novel bifunctional azaheterocyclic derivatives were obtained in yields up to 95%. In silico experiments on the molecular docking were performed to evaluate the binding possibility of the synthesized small azaheterocyclic molecules to the selected biotargets (BACE1, BChE, CK1δ, AChE) associated with the pathogenesis of neurodegenerative diseases. To assess the cytotoxicity for the synthesized compounds, a series of in vitro experiments were also carried out on healthy human embryo kidney cells (HEK-293). The leading compound bearing both 5-phenyl-4H-imidazole and 1-methyl-1H-indole moieties was defined as the prospective molecule possessing the lowest cytotoxicity (IC50 > 300 µM on HEK-293) and the highest binding energy in the protein–ligand complex (AChE, −13.57 kcal/mol). The developed compounds could be of particular interest in medicinal chemistry, particularly in the targeted design of small-molecule candidates for the treatment of neurodegenerative disorders.

Cite: Nikiforov E.A. , Vaskina N.F. , Moseev T.D. , Varaksin M.V. , Butorin I.I. , Melekhin V.V. , Tokhtueva M.D. , Mazhukin D.G. , Tikhonov A.Y. , Charushin V.N. , Chupakhin O.N.
Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay
Processes. 2023. V.11. N3. P.846. DOI: 10.3390/pr11030846 WOS Scopus РИНЦ

Dates:

Accepted:	Mar 7, 2023
Published print:	Mar 12, 2023
Submitted:	Mar 15, 2023

Identifiers:

Web of science	WOS:000958762900001
Scopus	2-s2.0-85151628875
Elibrary	61632206
OpenAlex	W4324053450

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