In Vitro and in Silico Studies of 3-Hydroxyflavone-Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α-Glycosidase Inhibitors

In this study, a novel series of sulfonate esters derived from 3-hydroxyflavone was synthesized and their inhibitory effects on acetylcholinesterase (AChE), α-glycosidase (AG), and carbonic anhydrase I and II (hCA I and II) enzymes were investigated using experimental and molecular docking analyses. The synthesis involved the reaction of 3-hydroxyflavone with tosyl chloride, mesytl chloride, β-naphthylsulfonyl chloride, and 8-quinolinesulfonyl chloride. The characterization of each compound was confirmed by obtaining 1H NMR, 13C NMR and IR spectra. Furthermore, IC50 and Ki values for the synthesized compounds were calculated and compared to the clinical enzyme inhibitors. Our results showed that the synthesized compounds exhibited inhibition against the targeted enzymes, with Ki values ranging from 1.92 to 4.16 nM for AChE, 32.40 to 55.49 nM for AG, 9.45 to 65.53 nM for hCA I, and 76.62 to 163.33 nM for hCA II. The compound involved quinolinesulfonyl moiety demonstrated especially potent inhibition with IC50 values of 3.96 nM for AChE, 32.40 nM for AG, 9.50 nM for hCA I, and 76.62 nM for hCA II. The docking results aligned well with our experimental findings. The findings have promising implications for the development of novel inhibitors and drug discovery efforts in the future.