Dataset DOI: 10.5061/dryad.4f4qrfjqh

Description of the data and file structure

The figures and tables presented here, along with the data presented in the main paper, provide comprehensive support for our research findings.

List of Figures (supplementary files in Zenodo)

Figure S1: Optimized geometries, HOMO, LUMO, and ESP of the selected aaptamines A12, A24, and A27.

Figure S2: Time dependent RMSD (nm) of the complexes of SAG@MAOB, TOL@COMT, and DON@AChE in the time range 500 ns.

Figure S3: (Top) Gyration radius (nm) and (Bottom) Root-mean-square of fluctuation RMSF (nm) of the complexes A12@MAOB, A24@COMT, and A27@AChE in comparison with the corresponding references.

Figure S4: Total energy of A12@MAOB, A24@COMT, and their references, SAG@MAOB and TOL@COMT, in relationship with the number of H-bonds of the complexes.

Figure S5: 2D and 3D images of the interactions in the complex conformation of: (A) A12, and (B) SAG with MAOB enzymes.

Figure S6: 2D and 3D images of the interactions in the complex conformation of: (A) A24, and (B) Tolcapone with COMT enzymes.

Figure S7: 2D and 3D images of the interactions in the complex conformation of Donepezil with AChE enzymes.

List of Tables

Description of files and variables:

Table S1: Molecular properties of Aaptamines set A (A1-A28).

• Cp: Compound
• N: Number of heavy atom
• TPSA (Å^2): Topological Polar Surface Area (Ų)
• MW (Dalton): Molecular weight (Dalton)
• NN,O: Number of hydrogen bond acceptor
• NNH,OH: Number of hydrogen bond donor
• nrotb: Number of rotatable bond
• V (Å^3): Volume (Å3)
• Lipinski violation

Table S2: ADMET properties prediction of set B (A1-A27).

• Cp: Compound

Absorption

• iLOGP: the logarithm of the octanol-water partition coefficient characterizes for lipophilicity of a molecule, calculated based on physics method
• WLOGP: the logarithm of the octanol-water partition coefficient characterize for lipophilicity of a molecule, calculated from atomistic method
• GI absorption: Gastrointestinal absorption
• Pgp substrate: Absorption on P-glycoprotein

Distribution

• BBB permeant: Blood Brain Barrier permeability
• Metabolism
• CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, and CYP3A4 inhibitor: Key Cytochrome P450 enzymes responsible for the metabolism of drugs

Excretion

• Total clearance (log ml/mim/kg): the body's overall ability to eliminate a drug
• Renal OCT2 substrate: Renal Organic Cation Transporter 2 substrate plays important role in the uptake of positively charged (cationic) drug from the blood into renal proximal tubule cells

Toxicity

• AMES toxicity: mutagenicity
• Max. tolerated dose (human) (log mg/kg/day)
• hERG I inhibitor: cardiotoxicity risk
• hERG II inhibitor: cardiotoxicity risk
• Oral Rat Acute Toxicity (LD50) (mol/kg)
• Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day)

Hepatotoxicity

• Skin Sensitisation
• T.Pyriformis toxicity (log ug/L)
• Minnow toxicity (log mM): environmental toxicity

Table S3: The main interactions, including conventional hydrogen bonding, carbon-hydrogen bonding, π-π stacked, and π-σ interactions of the most potent aaptamines for ND by molecular docking study. Values in parentheses indicate the distance of bonding or interaction (Å).

Code/software

All molecular optimized geometries are performed by Gaussian 16 package, revision A.03.

Molecular docking are performed with Autodock4.

Molecular dynamics are performed with Gromacs 2023.

Visualization of complex systems are illustrated with ChimeraX.