Rational design of novel diaryl ether-linked benzimidazole derivatives as potent and selective BACE1 inhibitors.

Due to the large size and high flexibility of the catalytic active site of BACE1 enzyme, the development of nonpeptide inhibitors with optimal pharmacological properties is still highly demanding. In this work, we have discovered 2-aminobenzimidazole-containg ether scaffolds having potent and selective inhibitory potentials against BACE1 enzyme. We have synthesized novel 29 compounds and optimization of aryl linker region resulted in highly potent BACE1 inhibitory activities with EC50 values of 0.05-2.71 µM. The aryloxy-phenyl analogs 20j showed the EC50 value as low as 0.07 µM in the enzyme assay, whereas, the benzyloxyphenyl dervative 24b was comparatively less effective in the enzyme assay. But interestingly the latter was more effective in the cell assay (EC50 value 1.2 µM). While comparing synthesized derivatives in the cell assay using PC12-APPSW cell, compound 27f appeared as the most potent BACE1 inhibitor having EC50 value 0.7 µM. This scaffold also showed high selectivity over BACE2 enzyme and cathepsin D. Furthermore, the research findings were bolstered through the incorporation of molecular docking, molecular dynamics, and DFT studies. We firmly believe that these discoveries will pave the way for the development of a novel class of small-molecule selective BACE1 inhibitors.

Extracting lignin from sugarcane bagasse for methylene blue and hexavalent chromium adsorption in textile wastewater: a facile, green, and sustainable approach.

This study presents the process of extracting lignin from sugarcane bagasse collected in the Mekong Delta, Vietnam by the alkali method. NaOH has been used as an effective, environmentally friendly chemical to enhance the extraction process. The obtained lignin was applied for methylene blue (MB) and hexavalent chromium (Cr(vi)) removal. Factors influencing lignin extraction and adsorption processes of MB and Cr(vi) were investigated, showcasing the sustainable reusability of lignin extracted from sugarcane bagasse. Lignin characterization was also carried out by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) techniques. The results showed that the extracted lignin content reached 38.61% under optimal conditions (NaOH concentration of 10%, reaction temperature of 90 °C and reaction time of 90 min). The adsorption efficiency and capacity of lignin reached 90.90% and 9.09 mg g-1 for MB and 80.10% and 28.04 mg g-1 for Cr(vi), respectively, under optimum adsorption conditions (pH, adsorption time, initial methylene blue concentration, and used lignin content). The adsorption process obeyed Langmuir adsorption and was principally physical adsorption. These findings prove sugarcane bagasse based lignin as a cheap and efficient adsorbent for MB and Cr(vi) removal, which contributes to the utilization of the abundant agricultural by-product for wastewater treatment.