Design, synthesis, biological evaluation, molecular docking, and dynamic simulation study of novel imidazo[2,1-b]thiazole derivatives as potent antioxidant agents

A series of novel hydrazinecarbothioamide and 1,2,4-triazole-3-thione derivatives of imidazo[2,1b]thiazole were synthesized and evaluated for their antioxidant activity. The antioxidant activity of 23 newly synthesized compounds and 10 previously reported compounds bearing similar scaffolds, were evaluated by DPPH radical scavenging activity. 4i, 4j, 4k, and 4n displayed the highest antioxidant activity which was comparable with the reference compound Quercetin. In addition to the in vitro analysis, docking studies targeting the active site of Human peroxiredoxin 5 (PDB ID: 1HD2) were employed to explore the possible interactions of these compounds with the receptor. Moreover, molecular dynamic simulations were performed. Molecular dynamic simulations confirmed the stability of the title compounds with 1HD2. Consequently, the obtained results displayed that 4i, 4j, 4k, 4n present a leading structure for future drug development due to its straightforward synthesis and relevant bioactivity. (c) 2022 Elsevier B.V. All rights reserved.