N-heterocyclic carbenes (NHCs) are chemical structures called heterocyclic structures that contain one or more nitrogen atoms. N-heterocyclic compounds are the basic building blocks of many drugs and biologically active molecules. One of these compounds is benzimidazolium salts. Herein, we present the synthesis of a series of phenylsulfonylethyl-substituted benzimidazolium salts. These compounds were characterized using NMR (1H- and 13C-) and FTIR spectroscopic techniques. Compound 1b exhibits a U-shaped benzimidazolium cation paired with a chloride anion. A hierarchical supramolecular architecture arises from C-H⋯Cl chains, C-H⋯π layers, and π⋯π stacking, demonstrating cooperative non-covalent stabilization of the crystal structure. The synthesized benzimidazolium derivatives exhibited notable inhibitory effect against human carbonic anhydrases (hCA I, hCA II)and acetylcholinesterase (AChE), with several compounds showing markedly lower Ki values than the clinical standards. Molecular docking of the NHCs with different receptors showed excellent binding capability with the active site of the target receptors. Moreover, the physicochemical and ADME analysis of the compounds were performed with SwissADME software. Overall examined compounds were found with very good oral bioavailability determined by Lipinski and Verber's rule. The compounds showed Pgp susceptibility with reasonable blood brain barrier permeability.

In this study, we report the synthesis and anticancer activities of new ruthenium complexes with N-heterocyclic carbene (NHC) ligands, which are of great significance for drug delivery research. For this reason, 4-methylsulfonylbenzyl-substituted benzimidazole-functionalized Ru(II)NHC complexes were synthesized in our research. The characterization of these new complexes were performed using appropriate spectroscopic methods (1H NMR, 13C NMR, and FT-IR) and elemental analysis techniques. The crystal structure of complex 1c was obtained using single crystal X-ray diffraction. MTT method was used to understand in vitro anticancer activities of the complexes against MCF-7 (breast cancer), HCT-116 (colon cancer), SH-SY5Y (brain cancer), and HeLa (cervical cancer) cell lines. Based on the IC50 values determined by MTT assay, the most effective complex was identified as 1 h. DNA binding analyses were carried out using agarose gel electrophoresis, revealing that 1 h weakly interacted with DNA. Additionally, the effects of 1 h on cell cycle progression and apoptosis in the SH-SY5Y cell line were examined using flow cytometry. The results indicated that 1 h induced G0/G1 phase accumulation and increased apoptotic cell death. These findings suggest that the synthesized complex 1 h has a significant anticancer potential.

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 1 H NMR, 13 C 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 mu M, 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.(c) 2022 Elsevier B.V. All rights reserved.

This study contains the synthesis of N-phthalimidomethyl-substituted NHC precursors and their Ag(I) NHC coordination compounds. The NHC precursors were synthesized from the 1-(N-phthalimidomethyl)benzimidazole and alkyl/aryl halide. The Ag(I)NHC coordination compounds were synthesized from the N-phthalimidomethyl substituted benzimidazolium salts and silver oxide via the in-situ deprotonation method. The formation of all compounds was proved fully by H-1 NMR, C-13 NMR, FTIR and elemental analysis techniques. Also, these novel N-phthalimidomethyl substituted NHC precursors and Ag(I) NHC coordination compounds were found as effective inhibitors for acetylcholinesterase (AChE), human carbonic anhydrase I isoenzyme (hCA I), human carbonic anhydrase II isoenzyme (hCA II), and butyrylcholinesterase (BChE) with inhibition constants (K(i)s) in the range of 1.00 +/- 0.14-2.31 +/- 0.58 mu M for hCA I, 1.30 +/- 0.21-2.85 +/- 0.56 mu M for hCA II, 0.35 +/- 0.06-2.58 +/- 0.70 mu M for AChE, and 0.42 +/- 0.01- 1.27 +/- 0.16 mu M for BChE, respectively. (C) 2020 Elsevier Ltd. All rights reserved.