Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading
cause of dementia and disability in the elderly. Despite extensive research, its
complete pathophysiology remains elusive. Current pharmacological treatments
primarily target the cholinergic hypothesis using acetylcholinesterase inhibitors
(AChEIs) and NMDA receptor antagonists. Known for its rich content of anthocyanins
and phenolic compounds, Thunbergia erecta has demonstrated potential AChE
inhibitory activity, particularly with vanillic acid and apigenin. This study aims to
evaluate the anticholinesterase activity of vanillic acid from T. erecta through in silico
testing and propose structural optimizations using molecular modeling. An in silico
screening was conducted using molecular docking techniques to evaluate the
interactions between vanillic acid derivatives and AChE. The strategy of maintaining
the hydroxyl-phenyl-carbonyl portion in the proposed structures proved effective,
providing hydrogen bonding interactions. The addition of aromatic side chains favored
π-π stacking interactions, and amine groups promoted π-alkyl interactions. Among the
12 proposed ligands, 6 were found to be promising, with compounds 5, 8, and 11
standing out.
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