Inclusion Complexation of Excavatin-A with β-Cyclodextrin: Stability, Water Accessibility, and Binding Affinity
Abstract
Excavatin-A (ExA) is one of the coumarin derivatives isolated from Clausena excavata roots. It exhibits promising biological activity and pharmacological properties. However, it has low solubility, causing limited usage in pharmaceutical applications. To cover this limitation, we investigated beta-cyclodextrin (βCD) as a potential host material for the ExA molecule with different conformations, which is the main objective of this work. Through molecular docking and molecular dynamics simulation, we evaluated the stability, water accessibility, and binding affinity of the inclusion complex. Percentage docked conformations (%DCs) of ExA inclusion complex towards BCD revealed two dominant conformations, A-form (70%) and C-form (30%). The results show that the A-form is the best conformation due to its stability and water accessibility within the hydrophobic cavity. Furthermore, the A-form demonstrated stronger binding free energy (∆Gbind) through the Molecular Mechanics-Poisson Boltzmann/Generalized Born Surface Area (MM-PB/GBSA) approaches with ∆Gbind(MM-GBSA): -25.84 kcal/mol and ∆Gbind(MM-PBSA): -23.31 kcal/mol. According to all the findings, βCD is a recommended material for ExA inclusion complexation with promising structural dynamics at the molecular level. The information on the inclusion complexation of ExA toward βCD is being reported for the first time in this work.