Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, and ADMET Studies of 4-Thiazolidinone Derivatives

Authors

Ashanul Haque
Mohd Wajid Ali Khan
Khalaf M Alenezi
Raoudha Soury
Muhammad S Khan
Shahzaib Ahamad
Md Mushtaque
Dinesh Gupta

Publication Date

1-9-2024

Journal

ACS Omega

Abstract

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-(2H-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.

Comments

Supplementary Materials

PMID: 38222574