Molecular Docking Insights into the Interaction of Cyclodextrin-Based Systems with Bioactive Monoterpenes of Biotechnological Interest

Abstract : Cyclodextrin-based systems are promising carriers for improving the stability and bioavailability of hydrophobic bioactive compounds. Monoterpenes, the major constituents of medicinal plant essential oils, exhibit significant pharmacological potential but are limited by poor aqueous solubility, high volatility, and chemical instability. This study investigated the structural and energetic interactions of sulfobutylether-β-cyclodextrin (SBE-β-CD) with the major bioactive constituents of essential oil of Alpinia zerumbet (EOAz), through molecular docking simulations. OEAz was obtained by hydrodistillation and complexed with SBE-β-CD (1:1 molar ratio) using the co-precipitation method. The resulting host–guest inclusion complexes, formed between SBE-β-CD and terpinen-4-ol or 1,8-cineole, were evaluated by molecular docking simulations. These compounds were selected based on their established status as major constituents of EOAz. Computational analyses were performed using HEX 8.0.0 software, followed by structural inspection in PyMOL. The docking results revealed energetically favorable interaction clusters, indicating high affinity and structural stability between the evaluated molecules. The most stable conformations demonstrated significant spatial complementarity and multiple intermolecular interactions, including hydrophobic contacts and hydrogen-bond-associated stabilization. Energetic analyses showed negative binding energies compatible with stable molecular association, supporting the formation of persistent host–guest complexes. Furthermore, the predicted host–guest interactions indicate that cyclodextrin complexation may favor the preservation of monoterpene integrity and bioavailability, factors that could contribute to enhanced or more consistent biological activity. Overall, these findings demonstrate the usefulness of molecular docking for investigating cyclodextrin-based systems and provide preliminar structural evidence for future studies exploring the therapeutic and biotechnological applications of monoterpene inclusion complexes.