Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, and ADMET Studies of 4-Thiazolidinone Derivatives
Ashanul Haque, Mohd Wajid Ali Khan, Mohd Wajid Ali Khan, Khalaf M. Alenezi, Raoudha Soury, Muhammad S. Khan, Muhammad S. Khan, Shahzaib Ahamad, Md. Mushtaque, Dinesh Gupta
Abstract
High Resolution Image Download MS PowerPoint Slide The design and development of new small-molecule glycation inhibitors are essential for preventing various chronic diseases, including diabetes mellitus, immunoinflammation, cardiovascular, and neurodegenerative diseases. 4-Thiazolidinone or thiazolidine-4-one is a well-known heterocyclic compound with the potential to inhibit the formation of advanced glycation end products. In the present work, we report the synthesis and characterization of four new 5-arylidene 3-cyclopropyl-2-(phenylimino)thiazolidin-4-one ( 1 – 4 ) compounds and their human serum albumin glycation inhibitory activity. One of the compounds 5-(2 H -1,3-benzodioxol-5-ylmethylidene)-3-cyclopropyl-2-(phenylimino)-1,3-thiazolidin-4-one ( 3 ) showed potent inhibition in the synthesis of initial, intermediary, and final products of glycation reactions. Besides, conformational changes in the α-helix and β-sheet (due to hyperglycemia) were also found to be reversed upon the addition of ( 3 ). Experimental findings were complemented by computational [molecular docking, ADME/Tox, and density functional theory (DFT)] studies. The docking scores of the compounds were in order 1 > 3 > 2 > 4, indicating the importance of the polar group at the 5-arylidene moiety. The results of ADME/Tox and DFT calculations revealed the safe nature of the compounds with high drug-likeness and stability. Overall, we speculate that the results of this study could provide valuable insights into the biological activity of 4-thiazolidinones.