Synthesis, molecular modelling and choline esterase enzyme inhibitory activity of novel enaminone derivatives of sulfonamides

Abstract

The enaminone derivatives of sulfonamides (1–11) were obtained in good yield and high purity. Choline esterase (ChE) inhibitory activities of the novel compounds against AChE and BChE were determined by Ellman’s method. Ki values of compounds for AChE and BChE enzymes were obtained in the ranges of 14.28˗160.17 µM, and 8.30˗324.27 µM, respectively. Compound, 9 presented good activity towards AChE and BChE with Ki values of 14.28 µM and 8.30 µM, respectively. Compounds 2 and 10 were found to be the most potent compounds showing cytotoxic effect (IC50 = 71.54 µg/mL and IC50 = 83.59 µg/mL), respectively, on lung cancer cell line (A549) and normal cells (Beas-2B) (IC50 = 164.62 µg/mL and IC50 = 155.64 µg/mL), respectively. The compounds have interacted with various proteins like AChE enzyme protein (PDB ID: 4M0E) and BChE enzyme protein (PDB ID: 5NN0). Finally, ADME/T analysis was performed to predict the movements of molecules in human metabolism. KEY WORDS: Sulfonamides, Enaminone, Enzyme inhibition, Molecular docking Bull. Chem. Soc. Ethiop. 2024, 38(5), 1351-1368.                                                      DOI: https://dx.doi.org/10.4314/bcse.v38i5.13