Synthesis, characterization, enzyme inhibition evaluations, and docking calculations of sulfonamide chalcone derivatives

The inhibition of enzymes is a highly practical area in drug development. In this study, twelve sulfonamide-containing chalcone derivatives (9–20) were synthesised. The inhibitory effects of these compounds on the isoenzymes carbonic anhydrase I (hCA I) and II (hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) were also investigated. These compounds demonstrated good in vitro inhibition of both hCA I and hCA II. They exhibited highly potent inhibitory effects on AChE and BChE (IC50 values ranging from 7.75 to 49.60 nM for AChE and 8.80 to 36.65 nM for BChE), and the results were compared with the standard inhibitor Tacrine (IC50: 34.65 nM for AChE and 26.65 nM for BChE). Of the compounds tested, compound 15 showed excellent in vitro inhibition of AChE (IC50: 7.75 nM) in the nanomolar range, while compound 20 showed the highest inhibition of BChE (IC50: 8.80 nM). To validate the experimental results, molecular docking simulations were performed for all synthesised compounds, which proved to be consistent. Examination of the results indicates that the sulfonamide chalcone derivatives have potential activity against the target enzymes AChE and BChE at the molecular level.