Synthesis and biological activities of chalcone derivatives

Abstract

Chalcones have drawn attention due to the simple structures and wide spectra of biological activities. Their core structure bearing diaryl rings with α,β-unsaturated ketone was generated easily using Claisen-Schmidt condensation. In this study, one hundred and eight chalcones and their derivatives were synthesized; among them, twenty-five were disclosed as new compounds. All synthesized chalcones were well-characterized by means of spectroscopy and evaluated for their anti-cancer (A549) and anti-inflammatory activities, and α-glucosidase inhibition. For anti-cancer activity, 3',4',5'-trimethoxyphenyl on the A ring, and hydroxy and methoxy groups on the B ring exhibited high potent inhibitory activity against A549 with three best potent compounds (4, 6, and 7). For anti-inflammatory activity, lead compounds including 2'-hydroxychalcone (34, 35, 42, 43, 45, and 48) and six 4'-aminochalcones (54, 55, 57, 58, 59, 70) showed high potent NO inhibitory activity without toxicity in LPS-induced RAW 264.7 macrophage cells. For α-glucosidase inhibitors, N-monoalkyl-4'-aminochalcones with the hydroxy group at meta and the methoxy at para position on the B ring (89, 91, 92) exhibited high α-glucosidase inhibitory activity with an uncompetitive inhibition mode. Moreover, E-arylidene steroids were investigated and three compounds (107, 108, 110) exhibited high potency as α-glucosidase inhibitors with mixed, noncompetitive, and competitive inhibition mode, respectively.