"Design, Molecular Docking, and Pharmacokinetic Evaluation of Thioimidazole-4-one Derivatives for Asthma Treatment"
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This study investigates the design, molecular docking, and ADME properties of thioimidazole-4-one derivatives as potential therapeutic agents targeting the A2A adenosine receptor for asthma treatment. Computational molecular docking was performed using the A2A receptor complexed with theophylline (PDB ID: 5MZJ), and the compounds were compared to theophylline to evaluate binding affinity. Docking results revealed that the synthesized compounds showed stronger binding affinities than theophylline, with several compounds (e.g., 5y and 3y) exhibiting superior PLP fitness scores. These compounds formed hydrogen bonds and hydrophobic interactions with key residues of the A2A receptor, such as ASN253, TYR271, and GLU169, suggesting their potential to modulate asthma-related mechanisms like airway constriction and inflammation. ADME analysis, conducted using the SwissADME server, indicated that compounds Y1–Y6 possessed favorable pharmacokinetic properties, including good gastrointestinal absorption, moderate bioavailability, and no P-glycoprotein interactions, making them suitable for oral administration. However, compounds Y7 and Y8 exhibited lower gastrointestinal absorption and increased polarity, suggesting the need for further structural optimization. The findings suggest that these thioimidazole-4-one derivatives are promising candidates for asthma therapy, with potential for further development based on their molecular docking results and ADME profiles.
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