We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a–j) and 13 benzimidazole-based Schiff bases 2 (a–m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a–j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a–m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.
Twenty-one analogs were synthesized based on benzimidazole, incorporating a substituted benzaldehyde moiety (1–21). These were then screened for their acetylcholinesterase and butyrylcholinesterase inhibition profiles. All the derivatives except 13, 14, and 20 showed various inhibitory potentials, ranging from IC50 values of 0.050 ± 0.001 µM to 25.30 ± 0.40 µM against acetylcholinesterase, and 0.080 ± 0.001 µM to 25.80 ± 0.40 µM against butyrylcholinesterase, when compared with the standard drug donepezil (0.016 ± 0.12 µM and 0.30 ± 0.010 µM, against acetylcholinesterase and butyrylcholinesterase, respectively). Compound 3 in both cases was found to be the most potent compound due to the presence of chloro groups at the 3 and 4 positions of the phenyl ring. A structure-activity relationship study was performed for all the analogs except 13, 14, and 20, further, molecular dynamics simulations were performed for the top two compounds as well as the reference compound in a complex with acetylcholinesterase and butyrylcholinesterase. The molecular dynamics simulation analysis revealed that compound 3 formed the most stable complex with both acetylcholinesterase and butyrylcholinesterase, followed by compound 10. As compared to the standard inhibitor donepezil both compounds revealed greater stabilities and higher binding affinities for both acetylcholinesterase and butyrylcholinesterase.
Zinc is an essential trace metal and its concentration above 4ppm reduces the aesthetic value of water. This study explores the possibility of using functionalized nanohybrids as Zn(II) ion scavengers from aqueous solution. Functionalized nanohybrids were synthesized by the attachment of thiosemicarbazide to silica. The material was characterized by TGA, SEM, FTIR, EDX, and BET analysis, which revealed ligand bonding to silica. The functionalized silica was employed as Zn(II) ion extractant in batch experiments and removed about 94.5% of the Zn(II) ions at pH 7, near zero point charge (6.5) in 30 min. Kinetics investigations revealed that zinc adsorption follows an intra particle diffusion mechanism and first-order kinetics (K = 0.1020 min−1). The data were fitted to Freundlich, Dubinin–Radushkevich, and Langmuir models and useful ion exchange parameters were determined. The impact of co-existing ions on Zn(II) ion sequestration was also studied and it was found that the adsorbent can be used for selective removal of zinc with various ions in the matrix. Quantum mechanical investigations revealed that the Zn(II) ion adsorption on ZnBS1 is more favorable, having higher binding energy (BE) (−178.1 kcal/mol) and ∆H (−169.8), and making tridentate complex with the N and S sites of the chelating ligand. The negative ∆G and BE values suggest highly spontaneous Zn(II) adsorption on the modified silica even at low temperatures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.