Synthesis, Characterization, Biological Evaluation and In Silico Studies of Some New Thiazole Derivatives

Background/Objectives: The thiazole ring is one of the core structures frequently favored in the design of new active compounds. Methods: A series of thiazole derivatives bearing a benzodioxole scaffold (1-9) were synthesized and evaluated for their antioxidant, anticholinesterase, and antidiabetic activities. Results: Antioxidant assays (ABTS and DPPH) revealed that compounds bearing 4-trifluoromethyl (compound 8) and phenyl (compound 9) moieties exhibited the strongest radical scavenging activities, attributed to efficient hydrogen atom transfer and extended π-conjugation, respectively. Enzyme inhibition studies showed that electron-withdrawing substituents such as 4-SO2CH3 (compound 3) and 3,4-diCl (compound 5) enhanced both AChE/BChE and α-amylase/α-glucosidase inhibition, surpassing the activity of acarbose in antidiabetic assays, while electron-donating groups reduced potency. Molecular docking and MD studies have shed light on the interactions of the active compounds. In addition, in silico ADMET predictions for the compounds have been performed. Conclusions: These results indicate that the thiazole-benzodioxole scaffold is a promising framework for developing multifunctional agents with combined neuroprotective, antidiabetic, and antioxidant activities.