Pyrimidine Derivatives Containing a Thiosemicarbazide Moiety as Potential Antioxidant and α-Glucosidase Inhibitors:...

In this study, a series of pyrimidine derivatives incorporating a thiosemicarbazide functional group were synthesized, and their structures were thoroughly characterized using ¹H NMR, ¹³C NMR, and HRMS. Biological assays demonstrate that compound 5a exhibits exceptional in vitro antioxidant activity, with IC₅₀ values of 3.96 µg/mL for DPPH radical scavenging and 2.01 µg/mL for ABTS radical scavenging, both of which are lower than those of the reference standards vitamin C (6.38 µg/mL) and trolox (8.04 µg/mL). Compound 5k shows significant in vitro α-glucosidase inhibitory activity, achieving an IC₅₀ value of 38.62 µg/mL, which is markedly lower than that of acarbose (237.48 µg/mL). Meanwhile, molecular docking results reveal that compounds 5a and 5k establish strong binding affinity to intermolecular interactions with the active site of the NADPH oxidase (PDB ID: 2CDU) and human intestinal α-glucosidase (PDB: 3TOP), respectively. Furthermore, molecular dynamics (MD) simulations indicate that compounds 5a and 5k forms stable interaction with the NADPH oxidase and human intestinal α-glucosidase, primarily driven by van der Waals forces. In addition, ADMET and drug-likeness analysis results show that the compound 5k is safety and possess favorable physicochemical properties suitable for potential drug candidate.