Computational study on the molecular inclusion of andrographolide by cyclodextrin

Area of Science:

• Computational chemistry
• Drug delivery
• Molecular modeling

Background:

• Andrographolide (andro) exhibits poor water solubility, limiting its bioavailability.
• Inclusion complexation with cyclodextrins (CDs) is a strategy to enhance solubility and bioavailability.
• No prior computational studies exist for andrographolide:cyclodextrin inclusion complexes.

Purpose of the Study:

• To computationally investigate the molecular inclusion modes between andrographolide and various cyclodextrins (alpha, beta, gamma).
• To identify the most stable inclusion complex structure and the driving forces behind its stability.
• To provide a computational basis for experimental studies and aid in new drug design.

Main Methods:

• Molecular docking using AutoDock.
• Density Functional Theory (DFT) and Austin Model 1 (AM1) calculations.
• Atoms-in-Molecules (AIM) analysis using B3LYP/cc-pVDZ wavefunction.

Main Results:

• Six possible inclusion complexes were analyzed.
• The most stable complex was identified as a 1:1 complex between andrographolide and beta-cyclodextrin (betaCD).
• The decalin ring moiety of andrographolide was found to be wrapped by betaCD, stabilized by intermolecular hydrogen bonds.

Conclusions:

• The computational findings are consistent with existing experimental data.
• The study elucidates the key interactions stabilizing andrographolide:betaCD inclusion complexes.
• This research can guide the development of improved drug formulations for andrographolide and similar compounds.