Design and synthesis of the 4H-chromenone derivatives against psoriasis

Abstract

On basis of Quercetin moiety, two series of 20 new compounds were designed and synthesized accordingly in this study, and their anti-inflammatory activities in vitro and in vivo were evaluated. At last, compound 8A2: 3- (1- (2- (4- (5-bromo-2-chlorobenzoyl) piperazin-1-yl) ethyl)-1H-1,2,3-triazol-4-yl) methoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one with low toxicity was found the best one for inhibiting of NO. Meanwhile, this compound could significantly inhibit the expression of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-α) and IL-17 (Interleukin-17), and also significantly down-regulate IL-17 mRNA psoriasis model in vitro. Further studies were performed to establish mouse psoriasis model induced by Imiquimod (IMQ), and the preliminary mechanism indicated that compound 8A2 may alleviate mouse psoriasis through obstructed the JAK1/2-STAT1/3 pathway. This study should be provide a basis for further study of effective treatment of psoriasis.

Keywords: 4H-chromenone derivative; Anti-inflammatory activity; JAK1/2-STAT1/3 pathway; Psoriasis.