Alzheimer's disease (AD) is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient's death. Despite the fact that novel pharmacological approaches endeavoring to block the neurodegenerative process are still emerging, none of them have reached use in clinical practice yet. Thus, palliative treatment represented by acetylcholinesterase inhibitors (AChEIs) and memantine are still the only therapeutics used. Following the multi-target directed ligands (MTDLs) strategy, herein we describe the synthesis, biological evaluation and docking studies for novel 7-methoxytacrine-p-anisidine hybrids designed to purposely target both cholinesterases and the amyloid cascade. Indeed, the novel derivatives proved to be effective non-specific cholinesterase inhibitors showing non-competitive AChE inhibition patterns. This compounds' behavior was confirmed in the subsequent molecular modeling studies.

• Keywords
• 7-methoxy-tacrine, Alzheimer’s disease, MTDLs, acetylcholinesterase, butyrylcholinesterase, tacrine,
• MeSH
• Acetylcholinesterase chemistry   MeSH
• Amyloid beta-Peptides antagonists & inhibitors   chemistry   MeSH
• Aniline Compounds chemical synthesis   chemistry   MeSH
• Cholinesterase Inhibitors chemical synthesis   chemistry   MeSH
• Kinetics MeSH
• Central Nervous System Agents chemical synthesis   chemistry   MeSH
• Humans MeSH
• Recombinant Proteins chemistry   MeSH
• Molecular Docking Simulation MeSH
• Tacrine analogs & derivatives   MeSH
• Binding Sites MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylcholinesterase MeSH
• Amyloid beta-Peptides MeSH
• Aniline Compounds MeSH
• Cholinesterase Inhibitors MeSH
• Central Nervous System Agents MeSH
• Recombinant Proteins MeSH
• Tacrine MeSH