Environment benign synthesis of 5-acyl-4-hydroxypyridin-2(1)-one derivatives as antioxidant and -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, , and displayed many folds higher antioxidants activity than the standard, BHT. The in vitro α-amylase inhibition was found to be moderate with IC values ranging from 5.48 to 9.31 mm as compared to the standard acarbose (IC = 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.