Solvent-free, microwave assisted, solid-catalyzed synthesis and α-glucosidase inhibition of chalcones

Abstract

A 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.