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A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC

The catalytic potential of pyridine-2-carboxlic acid has been evaluated for efficient, green and solvent free synthesis of 2,4,5-trisubstituted imidazole derivatives 3a-3m. The compounds 3a-3m were synthesized by one pot condensation reaction of substituted aromatic aldehydes, benzil, and ammonium acetate in good to excellent yields (74-96 %). To explore the potential of these compounds against Alzheimer's disease, their inhibitory activities against acetylcholinesterase (AChE) were evaluated. In this series of compounds, compound 3m, bearing one ethoxy and a hydroxy group on the phenyl ring on 2,4,5-trisubstituted imidazoles, proved to be a potent AChE inhibitor (102.56±0.14). Structure-activity relationship (SAR) of these compounds was developed. Molecular dockings were carried out for the compounds 3m, 3e, 3k, 3c, 3a, 3d, 3j, and 3f in order to further investigate the binding mechanism. The inhibitor molecule was molecularly docked with acetylcholinesterase to further study its binding mechanism. The amino group of the compound 3m forms an H-bond with the oxygen atom of the residue (i. e., THR121) which has a bond length of 3.051 Å.

We propose a new density functional for the evaluation of the total electronic energy by subtracting the Roothaan energy, i.e. the Hartree energy of the density residual, from the Hohenberg-Kohn-Sham (HKS) functional, which is normally used in self-consistent Kohn-Sham (KS) density functional theory (DFT) calculations. Because of the positive semi-definite nature of the Roothaan energy, the resulting Wang-Zhou (WZ) functional always produces a total energy lower than that from the HKS functional and usually converges to the exact total energy from below. Following the same spirit of the Zhou-Wang-λ (ZWλ) functional in the recently proposed orbital-corrected orbital-free (OO) DFT method (Zhou and Wang, J Chem Phys 2006, 124, 081107), we linearly mix the WZ functional with the HKS functional to allow further systematic error cancellations. The resulting Wang-Zhou-α (WZα) functional is compared with the ZWλ functional in OO-DFT calculations for systems within different chemical environment. We find that the optimal value of α for the WZα functional is more stable than that of λ for the ZWλ functional. This is because the WZ functional remedies the oscillatory convergence behavior of the Harris functional and renders the direct evaluation of α for the WZα functional more plausible in the application of the linear-scaling OO-DFT method for large systems. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem 107: 2995-3000, 2007