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

Authors: GONCA ÇELİK, GİZEM TATAR YILMAZ, HÜSEYİN ŞAHİN, BURAK BARUT, NURETTİN YAYLI

Abstract: 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-μ-D-glucopyranosylbromide) in dry acetone under the anhydrous condition at 0-5 °C. Deacylated was carried out by the Zemplen's method with NaOCH3 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 μ-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 μ-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.

Keywords: Chalcone, enzyme inhibition, glycoside, glycosylation, molecular docking

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