Bridge, N-heterocyclic Carbene Complexes with Silver (I) and Palladium (II): Synthesis and Biological Activity

The present study describes synthesis, characterization (UV-Vis, FT-IR, 1HNMR, CHN analysis and melting point) and biological activity of new substituted benzimidazolium salt and their N-heterocycliccarbene (NHC) respective Ag(I) and Pd(II) complexes. The benzimidazole reacted with acetamide substituents at 90oC to form variety substituted of benzimidazolium salt to yield unsymmetrically substituted salt. Silver(I) complex was synthesized from the reaction of unsymmetrical substituted benzimidazolium salt with Ag2O using in-situ deprotonation technique to give derived structures in good yield.The use of Ag(I)-NHC complex is as transfer reagents by using the transmetallation technique to prepare respective Pd(II)-NHC. The biological activity. of the formed substituted benzimidazolium salts, Ag(I) and Pd(II) complexes was estimated against some bacteria strains S. aureus. And E.coli .The Ag(I)showed good activity while their corresponding salt and Pd(II)-NHC complex show less activity.

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by 1H-NMR, 13C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC50 value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC50 value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC50 = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.

Docking-designed Green Synthesis and In-Vitro Anticancer Studies of New Binuclear Se-N-Heterocyclic Carbene Adducts and their Azolium Salts

Two binuclear selenium adducts (5 and 6) were designed using molecular docking approach while finding their promising interaction to four angiogenic factor-proteins including COX-1 (Cyclooxygenase-1), VEGF-A (vascular endothelial growth factor A), HIF (Hypoxia-inducible factor) and EGF (human epidermal growth factor). They were consequently synthesized using In-situ coordination approach. The green synthetic approach was employed for coordination as it was carried out in water instead of organic solvents. The synthesized adducts as well as their respective bis-benzimidazolium salts (2 and 4) were confirmed by 1H and 13C-NMR along with FT-IR spectroscopy. The both were, then, subjected to In-vitro anticancer activities against breast adenocarcinoma cell line (MCF-7), cervical cancer cell line (Hela), mouse melanoma cell line (B16F10) and retinal ganglion cell line (RGC-5) using MTT assay while comparing their activities with a commercially established standard-drug 5-Fluorouracil. However, the exceptional activities of both adducts and bis-benzimidazolium salts were explored.

Synthesis of Xylyl-Linked Bis-Benzimidazolium Salts and Their Application in the Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction of Aryl Chlorides

A new series of xylyl-linked bis-benzimidazolium salts were efficiently prepared using a simple preparation method from bis-benzimidazolium precursors featuring highly tunable linkers and wingtips. A highly efficient Suzuki–Miyaura cross-coupling reaction of aryl chlorides within the range of 0.5–2.0 mol% Pd-catalyst loading was observed. Also, di-ortho-substituted biaryl synthesis was achieved.

Synthesis, characterization, and in silico analysis against SARS CoV-2 of novel benzimidazolium salts

In acute conditions, vaccines are very important, although they provide antibodies for fighting against COVID-19 for a certain period. It is necessary to produce an anti-viral agent for a usual healing process against SARS CoV-2 which is responsible the pandemic we are living in. Many drugs with benzimidazole main scaffold are still used in a wide variety of treatment procedures. In this case, substituted benzimidazole structures could be good candidates for fighting against COVID-19. Theoretical calculation methods could be a key tool for overcome the difficulties of individual analyzing of each new structure. In this study, new benzimidazole structures were synthesized and characterized for in silico evaluation as anti-viral agent. The molecules were optimized and analyzed for reactivity with Koopmans Theorem. Also, molecular docking simulations were performed for SARS coronavirus main peptidase (PDB ID: 2GTB), COVID-19 main protease (PDB ID: 5R82), and papain-like protease of SARS CoV-2 (PDB ID: 6W9C) crystals.

Benzimidazolium Salts Bearing 2-methyl-1,4-benzodioxane Group: Synthesis, Characterization, Computational Studies, In vitro Antioxidant and Antimicrobial Activity

This study contains the synthesis of the 1-(2-methyl-1,4-benzodioxane)benzimidazole and 2-methyl-1,4-benzodioxane substituted benzimidazolium salts. The benzimidazolium salts were synthesized from the reaction of the 1-(2-methyl-1,4-benzodioxane)benzimidazole and various aryl chlorides. All compounds were characterized using 1H NMR, 13C NMR, FTIR spectroscopy, and elemental analysis techniques. The antioxidant properties of benzimidazolium salts were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and hydrogen peroxide scavenging ability assays. The compounds showed a moderate inhibitory effect on DPPH radical (The percent inhibition = 29.53-39.75). Also, the compounds exhibited significant H2O2 radical scavenging activity. Antimicrobial activities of the compounds were examined against nine bacterial strains and Candida albicans. All compounds displayed marked antimicrobial activity against tested microorganisms, particularly against Pseudomonas aeruginosa, Listeria monocytogenes, and C. albicans. From the computational perspective, benzimidazolium salts were also optimized at B3LYP / DMol3// DFT level using the Discovery Studio 2020 program. HOMO–LUMO analysis and molecular electrostatic potential surface (MESP) were exerted to examine the effects of benzimidazolium salts' electronic and structural properties.