Synthesis and Biological Evaluation of A Novel Series of Chalcone Derivatives as Enzyme Inhibitors and Antioxidant Agents

Abstract

A series of chalcone-sulfonate analogs bearing bromo substituents (A1-A10) were successfully synthesized and structurally characterized by utilizing ¹H NMR, ¹³C NMR, and HRMS. The compounds (A1-A10) were screened for their acetylcholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities and in vitro antioxidant activity. Compounds A8 (0.266 ± 0.06 mM) and A3 (0.274 ± 0.06 mM) exhibited high AChE inhibition levels, as evidenced by their low IC₅₀ values, which are comparable to that of the positive reference, tacrine (0.230 ± 0.07 mM). Compound A9 was found to be the effective inhibitor of PL in both in silico (−10.7 kcal/mol) and in vitro (IC₅₀: 0.522 ± 0.08 mM) studies. Also, the most effective molecular docking interaction of AChE was found with the compounds A3 (−11.7 kcal/mol) and A8 (−11.6 kcal/mol). Furthermore, the antioxidant activities of the compounds (A1-A10) were found to be low based on the ABTS and DPPH radical scavenging assays. In contrast, their antioxidant activities were measured to be high in the FRAP assay and moderate in the CUPRAC assay. Among these, compound A9 exhibited the most potent antioxidant activity, with values of 0.689 ± 0.087 BHA equivalents in the FRAP assay and 0.315 ± 0.073 BHA equivalents in the CUPRAC assay. The results of this study indicate that the novel chalcone compounds exhibit moderate to good enzyme inhibitory and antioxidant activities, suggesting their potential for inclusion in further supportive and exploratory studies.