Solvent‐free, microwave‐assisted, solid‐catalyzed synthesis and α‐Glucosidase inhibition of chalcones

Abstract

AbstractA series of chalcone analogues were synthesized using Claisen‐Schmidt condensation and assayed for in vitro inhibitory activity against α‐glucosidase. The synthesis involved in solvent‐free reaction conditions including NaOH‐catalyzed grinding or microwave irradiation in the presence of a clay‐based catalyst. Hydroxychalcones and 2′‐hydroxychalcones were not isolated when using grinding method, while the microwave‐assisted, clay‐catalyzed synthesis gave these desired products. In addition, flavanones, cyclization products from 2′‐hydroxychalcones were formed in both methods. Flavanones 3g and 3s were the most active toward α‐glucosidase. Compound 3g exhibited an effect (IC50 = 10.4±0.2 μM) close to genistein (IC50 = 7.8±0.3 μM), a known α‐glucosidase inhibitor. Structure‐activity relationship analysis indicated that the 4‐hydroxy substituted motif in ring B of chalcones seems to be an important factor on the α‐glucosidase inhibitory activity. Furthermore, the 3,4‐difluorinated chalcones also exhibited activities as compared to mono‐fluorinated derivatives, suggesting that the more fluorination in ring B may be crucial for the inhibitory activity.