Environment benign synthesis of 5-acyl-4-hydroxypyridin-2(1H)-one derivatives as antioxidant and α-amylase inhibitors.

Aim: Oxidative stress, caused by postprandial activities, is a major global health issue causing chronic diseases like diabetes mellitus, cancer, and asthma. Therefore, it was envisaged to design and synthesize a series of substituted 4-hydroxypyridine-2(1 h)-ones in order to develop new molecules that can reduce oxidative stress and modulate α-amylase activity also.

Materials & methods: An environmentally benign, solvent and catalyst free, natural product inspired synthesis of 4-hydroxypyridin-2(1 h)-one derivatives has been developed. The synthetic analogues were evaluated in vitro α-amylase activity and antioxidant potential.

Results: Among all the synthesized compounds, 4a, 4c, and 4d displayed many folds higher antioxidants activity than the standard, BHT. The in vitro α-amylase inhibition was found to be moderate with IC₅₀ values ranging from 5.48 to 9.31 mm as compared to the standard acarbose (IC₅₀ = 0.65 mm). The most active compound against α-amylase 4c was further investigated for its binding affinity within the active site of the enzyme and the kinetics studies revealed probable uncompetitive mode of inhibition.

Conclusion: Compound 4a was found to be promising antioxidant and 4c as a good α-amylase inhibitor. These compounds could pave the way for development of new α-amylase inhibitors with antioxidant capabilities thereby effectively mitigating diabetes mellitus.