Computational Screening of Columbianadin-Derived Furanocoumarins as Multitarget Neurotherapeutics Against MAO-B, AChE, and BACE1 For Alzheimer's Disease
In silico study reveals Columbianadin-derived furanocoumarins as multitarget inhibitors of MAO-B, AChE, and BACE1, suggesting a potential scaffold for Alzheimer's disease therapeutics.
Key Points
To computationally screen Columbianadin-derived furanocoumarins against monoamine oxidase B (MAO-B), acetylcholinesterase (AChE), and β-secretase 1 (BACE1) to identify natural multi-target neurotherapeutics for Alzheimer's disease.
Screened PubChem furanocoumarin derivatives for central nervous system likeness, pharmacokinetics, and toxicity profiles.
Performed cross-docking and MM-GBSA rescoring across MAO-B, AChE, and BACE1 using FRED and Glide scoring engines.
Evaluated complex stability through 200 ns molecular dynamics simulations in DESMOND and calculated electronic reactivity profiles via density functional theory.
Identified compound PubChem ID 132962208 as the top multi-target candidate consistently prioritized across all three docking scoring engines.
Demonstrated sustained ligand-target interactions and minimal conformational fluctuations across a 200 ns molecular dynamics simulation.
Confirmed electronic stability and drug-like reactivity profiles through frontier molecular orbital and HOMO–LUMO gap analyses.