Design, synthesis, and enzyme inhibition evaluation of some novel Mono- and Di-O-β-D-Glycopyranosyl Chalcone analogues with molecular docking studies

In this study, some novel mono- and di-O-β-D-glycopyranosyl chalcone analogs were designed, synthesized, and characterized. The chalcone derivatives were synthesized with good yields by base-catalyzed Claisen-Schmidt condensation in EtOH solution. Then these chalcones were reacted with TAGBr (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosylbromide) in dry acetone under the anhydrous condition at 0–5 °C. Deacylated was carried out by the Zemplen’s method with NaOCH(3) in dry methanol results in substituted chalcone-O-glycosides (mono- and di-O-β-D-glycopyranosyl chalcone analogs). The chemical structures of all synthesized compounds were elucidated based on IR, NMR spectral data, and mass spectrometry. Further, the compounds (7a–c, 8a–c, 12a–c, 16a–c, and 17a–c) were tested for their enzyme inhibition activity against α-glycosidase, tyrosinase, and AChE with in vitro and in silico analysis. Amongst them, compounds 12a–c, 16a–c, and 17a–c displayed moderate or less enzyme inhibition activity against α-glycosidase while other compounds 7a–c and 8a–c) were not active. Remarkably interesting enzyme inhibition effects, with IC(50) values below 30.59 ± 0.30 μM were recorded with 7c (IC(50)=11.07 ± 0.55 μM) against tyrosinase.