Synthesis of new carboxylates and sulfonates containing thiazolidin-4-one ring and evaluation of inhibitory properties against some metabolic enzymes

A series of thizaolidin-4-one derivatives (3a-o) was synthesized with excellent yield (94-97%) and the structures of the compounds were characterized with Fourier-transform Infrared (FTIR), Nuclear Magnetic Resonance (H-1 NMR-C-13 NMR), and High-resolution Mass Spectroscopy (HRMS). Novel compounds were tested towards some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I-II (hCA I-II). All the synthetic analogs had potent inhibitory strength with Ki values in the range of 161.28 +/- 16.91-943.13 +/- 57.23nM against hCA-I and 151.77 +/- 21.42-879.89 +/- 57.70 nM against hCA-II in comparison to the standard acetazolamide K-i = 847.18 +/- 75.41nM (for hCA-I) and Ki = 776.12 +/- 70.62nM (for hCA-II). Most of the compounds showed potent inhibitory activity against AChE and BChE enzymes with IC50 value 823.71-984.32 nM, 321.88-879.02 nM, 2.61-83.08 nM compared to the standard compounds (928.85, 691.41, and 68.85 nM), respectively. Additionally, the molecular docking study was carried out for the most active compound for the determination of ligand-enzyme interactions. Also, the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME/T) properties of the molecules were calculated. [GRAPHICS] .