Preferential inhibition of α-amylase by cinnamaldehyde-based hydrazones: A comparative study.

The escalating issue of obesity and related health conditions, including diabetes mellitus and coronary heart disease, necessitates the development of digestive enzyme inhibitors. Targeting pancreatic lipase to inhibit fatty acid generation to attain reduced lipid absorption is a promising approach for identifying effective agents. Orlistat, the only clinically approved pancreatic lipase inhibitor, is associated with gastrointestinal side effects like oily stools, spotting, and flatulence. Concurrently, α-amylase inhibitors can mitigate rapid spikes in blood sugar levels. With the growing significance of natural products in pharmaceutical research, cinnamaldehyde has been recognized as a potential enzyme inhibitor. This study explores the effects of cinnamaldehyde-derived hydrazone Schiff bases on lipase and α-amylase through in vitro experiments. The synthesized compounds exhibited IC50 value for lipase in the same range ((0.41-12.58) × 10-8 M) as exhibited by the commercial drug orlistat (5.76 × 10-8 M). However, for α-amylase inhibition, the compounds (IC50 value = 0.37-9.54 × 10-9 M) were found effective inhibitors of acarbose (IC50 value = 6.76 × 10-6 M) and curcumin (IC50 value = 467 × 10-9 M). In silico DFT studies, molecular docking, drug likeliness, bioactivity score, ADME, and toxicity are also investigated for these compounds.