Theoretical Investigation of Cyclodextrin Encapsulation to Enhance the Solubility of Ethionamide and Its Synergistic Boosters
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Abstract
Multidrug-resistant tuberculosis (MDR-TB) remains a global health challenge, necessitating novel strategies to improve the effectiveness of existing second-line treatments. Ethionamide, a key antitubercular agent, suffers from poor solubility, low oral bioavailability, and formulation challenges due to its crystalline nature. Synergistic booster compounds such as BDM43266 have been developed to enhance ethionamide bioactivation, but they face similar pharmacokinetic limitations. This study investigates the potential of native cyclodextrins (𝛼-CyD, and 𝛽-CyD) to form inclusion complexes with ethionamide and its synergistic boosters using molecular modelling approaches. Molecular docking and complexation energy calculations were conducted to assess binding stability and host–guest interactions. The results reveal that 𝛽-CyD forms the most stable complexes with ethionamide and selected boosters, particularly BDM41907 and BDM41906, due to optimal steric fit and favourable interaction energies. These findings support the use of cyclodextrin-based drug delivery systems to improve the solubility and therapeutic performance of ethionamide and its synergistic boosters in MDR-TB treatment.
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