Chalcone-sulfonate ester derivatives as dual urease and α-amylase inhibitors: synthesis, biological evaluation and integrated computational studies

A series of chalcone-sulfonate ester derivatives (1-7) were synthesized and evaluated for their potential inhibitory activity against urease and α-amylase enzymes. The chemical structures of the synthesized compounds were confirmed using appropriate spectroscopic techniques (IR, NMR and mass spectrometry). The biological potential of these derivatives was assessed through in vitro enzyme inhibition assays, where several compounds demonstrated promising activity against both urease and α-amylase, suggesting their possible application in the management of urease-related infections and disorders associated with carbohydrate metabolism. Structure-activity relationship (SAR) analysis revealed that the nature and position of substituents on the aromatic rings significantly influenced the inhibitory potency of the compounds. To further understand the interaction mechanisms, molecular docking studies were performed to investigate the binding modes of the synthesized molecules within the active sites of the target enzymes. In addition, pharmacokinetic properties were evaluated through in silico ADME analysis to assess drug-likeness and potential bioavailability. Furthermore, molecular dynamics (MD) simulations were carried out to examine the stability and dynamic behaviour of the ligand-enzyme complexes, while density functional theory (DFT) calculations were employed to explore the electronic characteristics and reactivity parameters of the compounds. The integrated experimental and computational findings highlight the potential of chalcone-sulfonate esters as promising scaffolds for the development of novel urease and α-amylase inhibitors.