Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay

Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay Full article

Journal

Processes
ISSN: 2227-9717

Output data

Year: 2023, Volume: 11, Number: 3, Pages: 846 Pages count : 1 DOI: 10.3390/pr11030846

Tags

azaheterocycles; indoles; imidazoles; C-H functionalization; nucleophilic substitution of hydrogen; PASE; in vitro cytotoxicity assay; neurodegenerative diseases; molecular docking

Authors

Nikiforov Egor A. ¹ , Vaskina Nailya F. ¹ , Moseev Timofey D. ¹ , Varaksin Mikhail V. ^1,2 , Butorin Ilya I. ¹ , Melekhin Vsevolod V. ^1,3 , Tokhtueva Maria D. ¹ , Mazhukin Dmitrii G. ⁴ , Tikhonov Alexsei Y. ⁴ , Charushin Valery N. ^1,2 , Chupakhin Oleg N. ^1,2

Affiliations

1	Федеральное государственное автономное образовательное учреждение высшего образования «Уральский федеральный университет имени первого Президента России Б.Н. Ельцина».
2	Federal State Institution of Science Institute of Organic Synthesis , Ural Branch of the Russian Academy of Sciences
3	Department of Medical Biology and Genetics, Ural State Medical University
4	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences

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.

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 OpenAlex

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

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

DB	Citing
OpenAlex	4
Web of science	4
Scopus	3