Design, Synthesis, and Biological Activity of Novel Quinone Derivatives as Potent STAT3 Inhibitors for Psoriasis Treatment

Psoriasis, which severely affects the sufferer's life quality, is a chronic skin disease still lacking satisfactory medication. Recently, signal transducer and activator of transcription 3 (STAT3) was revealed playing an important role in the progression of psoriasis. In this paper, a total of 59 quinone derivatives with various scaffolds were designed, synthesized, and evaluated for antipsoriatic potential as STAT3 inhibitors. Among them, <b>15e</b> was identified as the most potent antipsoriatic agent and could bind to STAT3; reduce both total and phosphorylated STAT3 levels, inhibit the nuclear translocation of STAT3; and, therefore, inhibit the transcription and expression of the propsoriatic factor IL-17A. <i>In vivo</i> experiments on mice showed that the topical application of <b>15e</b> was effective in alleviating IMQ-induced psoriasis without noticeable side effects. In all, this research rendered <b>15e</b> as a promising drug candidate for psoriasis.