Synthesis, Characterization, X-ray Crystallography, Acetyl Cholinesterase Inhibition and Antioxidant Activities of Some Novel Ketone Derivatives of Gallic Hydrazide-Derived Schiff Bases

Abstract

Alzheimer's disease (AD) is the most common form of dementia among older people and the pathogenesis of this disease is associated with oxidative stress. Acetylcholinesterase inhibitors with antioxidant activities are considered potential treatments for AD. Some novel ketone derivatives of gallic hydrazide-derived Schiff bases were synthesized and examined for their antioxidant activities and in vitro and in silico acetyl cholinesterase inhibition. The compounds were characterized using spectroscopy and X-ray crystallography. The ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays revealed that all the compounds have strong antioxidant activities. N-(1-(5-bromo-2-hydroxyphenyl)-ethylidene)-3,4,5-trihydroxybenzohydrazide (2) was the most potent inhibitor of human acetyl cholinesterase, giving an inhibition rate of 77% at 100 μM. Molecular docking simulation of the ligand-enzyme complex suggested that the ligand may be positioned in the enzyme's active-site gorge, interacting with residues in the peripheral anionic subsite (PAS) and acyl OPEN ACCESSMolecules 2012, 17 2409 binding pocket (ABP). The current work warrants further preclinical studies to assess the potential for these novel compounds for the treatment of AD.

Benzamide Derivatives as Potential Candidates for Anti-Alzheimer, Anti-Fatigue, Anti-Urease and Anti-Oxidant Activity

“…Compounds 3a and 3g exhibited the highest activity which could be ascribed to the increased of resonance effect caused by electrons of the nitrogen attached linked with aromatic ring [26].…”

New Hydrazones Bearing Thiazole Scaffold: Synthesis, Characterization, Antimicrobial, and Antioxidant Investigation

“…(7): yellow powder, yield: 87%, mp: 232 °C. (8) (9): yellow powder, yield: 86%, mp: 290 °C. (10): light yellow powder, yield: 98%, mp: 289 °C.…”

“…New series of hydrazones have been synthesized and investigated for their antitumor, antioxidant [9], and antimicrobial activities [10][11][12][13].…”

Synthesis of novel Schiff base derivatives of tacrine and investigation of their acetylcholinesterase inhibition potency

“…The greatest inhibition potency was obtained from 3a. In the literature, there are a few studies of Schiff base derivatives of AChE inhibitors [27,42,43]. So, this work can contribute for synthesizing new Schiff base derivatives of AChE inhibitors and points a way to potential new therapies of AD.…”