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, 15e 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. In vivo experiments
on mice showed that the topical application of 15e was
effective in alleviating IMQ-induced psoriasis without noticeable
side effects. In all, this research rendered 15e as a
promising drug candidate for psoriasis.