title: 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 binding pocket (ABP). The current work warrants further preclinical studies to assess the potential for these novel compounds for the treatment of AD.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia. nura_suleiman@siswa.um.edu.my
authors.forename: Nura Suleiman
authors.initials: NS
authors.lastname: Gwaram
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.forename: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
authors.forename: Michael J C
authors.initials: MJ
authors.lastname: Buckle
authors.forename: Sri Devi
authors.initials: SD
authors.lastname: Sukumaran
authors.forename: Lip Yong
authors.initials: LY
authors.lastname: Chung
authors.forename: Rozana
authors.initials: R
authors.lastname: Othman
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Alhadi
authors.forename: Wageeh A
authors.initials: WA
authors.lastname: Yehye
authors.forename: A Hamid A
authors.initials: AH
authors.lastname: Hadi
authors.forename: Pouya
authors.initials: P
authors.lastname: Hassandarvish
authors.forename: Hamid
authors.initials: H
authors.lastname: Khaledi
authors.forename: Siddig Ibrahim
authors.initials: SI
authors.lastname: Abdelwahab
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D020816:Amino Acid Motifs; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D006834:Hydrazines; D007659:Ketones; D012545:Schiff Bases; D000110:Acetylcholinesterase