Ethyl 2‐cyano‐3‐pyrazolylacrylates as Digestive Enzyme Inhibitors: In Vitro and Computational Assessment

ABSTRACT Obesity, a chronic illness, is associated with long‐term disability, hospitalization, diminished quality of life, and mortality, serving as a risk factor for numerous chronic ailments, such as hypertension, elevated cholesterol levels, stroke, heart disease, kidney disease, amputation, specific cancers, and arthritis. Therefore, there is a pressing need for new anti‐obesity agents. Thus, a series of pyrazole 4‐carbaldehydes and their cyanoacrylate derivatives were synthesized and evaluated for their inhibitory potential against α‐amylase, lipase, and trypsin enzymes, along with their serum protection efficacy. Comparative structure‐activity relationship analysis revealed that meta‐substituted cyanoacrylates exhibited markedly superior α‐amylase and lipase inhibitory activities than their para‐substituted analogs, exemplified by compounds ethyl‐2‐cyano‐3‐(3‐(3‐nitrophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)acrylate (53.42%) and ethyl‐3‐(3‐(3‐chlorophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐2‐cyanoacrylate (51.46%), respectively. Furthermore, in the statistical analysis, the F ‐values and p ‐values were as follows: trypsin – F = 38.35974, p < 0.0001; amylase – F = 99.26896, p < 0.0001; lipase – F = 9.866327, p < 0.0001; and SPp – F = 37.52078, p < 0.0001.