Synthesis, characterization and inhibitor properties of benzimidazolium salts bearing 4-(methylsulfonyl)benzyl side arms

• Published in: Journal of molecular structure 2023-02, Vol.1273, p.134320, Article 134320
• Main Authors: Güzel, Abdussamat, Noma, Samir Abbas Ali, Şen, Betül, Kazancı, Ali, Taskin-Tok, Tugba, Kolaç, Turgay, Aktaş, Aydın, Ateş, Burhan, Aygün, Muhittin, Gök, Yetkin
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Benzimidazolium salt; Molecular docking; Single-crystal; Sulfonyl; Xanthine oxidase
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.134320

•Benzimidazolium salts bearing 4-(methylsulfonyl)benzyl group were synthesized.•All compounds were characterized by NMR and FTIR spectroscopic techniques.•Two compounds were examined by the single-crystal X-ray diffraction method.•Inhibitory effects of all compounds were been tested against XO and AChE enzymes.•Molecular docking work was conducted on the chosen compounds against AChE and XO. [Display omitted] Herein, a series of N-heterocyclic carbene (NHC) precursors bearing sulfonyl moieties was prepared. These compounds were characterized by using 1H NMR, 13C NMR, FT-IR spectroscopy and elemental analysis techniques. Molecular and crystal structures of two compounds were determined by using the single-crystal X-ray diffraction method. Furthermore, enzyme inhibitory properties of benzimidazolium salt were tested against xanthine oxidase (XO) and acetylcholinesterase (AChE). Docking applications were used by using AutoDock4 in order to define the binding pose of the selected compounds, and also to visualize the correlation of the generated optimal complexes. Herein, a series of N-heterocyclic carbene (NHC) precursors bearing sulfonyl moieties was prepared. 1-(4-(methylsulfonyl)benzyl)-3-alkylbenzimidazolium chloride salts were synthesized with the reaction of 1-alkylbenzimidazoles with 4-(methylsulfonyl)benzyl chloride. These compounds were characterized by using 1H NMR, 13C NMR, FT-IR spectroscopy and elemental analysis techniques. Molecular and crystal structures of compounds 2e and 2j were determined by using the single-crystal X-ray diffraction method. Furthermore, enzyme inhibitory properties of benzimidazolium salt were tested against xanthine oxidase (XO) and acetylcholinesterase (AChE), then determined the IC50 value range of XO were determined from 0.218 to 1.927 µM, while the IC50 for AChE were determined from 1.328 to 5.22. Docking applications were used by using AutoDock4 in order to define the binding pose of the selected compounds, (2c, 2d and 2g) and also to visualize the correlation of the generated optimal complexes. It is found that the compound 2g has good binding affinity (-11.24 kcal/mol) against AChE, on the other side, compound 2c shows the lowest binding energy (-8.32 kcal/mol) for the XO target. These findings and the defined compounds could be as potential agents to develop effective medicine for AChE and XO in the future.