Design, synthesis and molecular docking studies of 5-fluoro 1-aryl/alkyl sulfonyl benzimidazole derivatives for treatment of Parkinson’s disease

Novel sulfonyl derivatives of 5-fluoro-substituted benzimidazole were synthesized and characterized by 1H-NMR, 13C-NMR, 19F-NMR and mass spectrometry. Molecular docking study against monoamine oxidase B (MAO-B), responsible for Parkinson’s disease (PD), was performed. The binding energy and interactions with active amino acid residues in the binding site of newly synthesized derivatives, as well as conventional inhibitors (Selegiline and Rasagiline), were investigated and presented. According to the docking scores predicted by ADV (AutoDock vina) and AD (AutoDock), most of the synthesized derivatives have higher binding affinity toward MAO-B than the conventional inhibitors. This study shows that these fluoro-substituted benzimidazole derivatives can be developed into essential drugs for the treatment of PD. The antibacterial property of these compounds was investigated by disk diffusion test and minimum inhibitory concentration (MIC), against gram-negative and gram-positive bacteria. And the results were further verified by the bacteria kill test with respect to time. All the synthesized compounds demonstrated considerable antibacterial activity against both bacterial strains. Therefore, this work focuses on defining the efficiency of different types of sulfonyl derivatives of fluorinated benzimidazole in biomedical research for the treatment of PD highlighting their versatile biological properties.</p

Reduced-Phenalenyl-Based Molecule as a Super Electron Donor for Radical-Mediated C–N Coupling Catalysis at Room Temperature

We demonstrate that an in situ generated di-reduced phenalenyl (PLY) species accumulates sufficiently high energy and acts as a super electron donor to generate aryl radicals from aryl halides to accomplish Buchwald–Hartwig-type C–N cross-coupling reactions at room temperature. This catalytic protocol does not require any external stimuli such as heat, light, or cathodic current. This protocol shows a wide variety of substrate scope covering different genres of aryl and heteroaryl halides with various aromatic as well as aliphatic amines and late-stage functionalization of the well-known natural products. The control experiments, along with extensive density functional theory (DFT) calculations, unveil that the aryl radical is generated by a single electron transfer from the di-reduced PLY to the aryl halide substrate. The aryl radical acts as an electrophile and binds with amine, leading to the chemically driven radical-mediated C–N cross-coupling under transition-metal-free conditions