LAUSR

ABSTRACT The therapeutic efficacy of topically applied azaphenothiazine derivatives: 9‐chloro‐6‐acetylaminobutylquinobenzo[3,2‐b][1,4]thiazine (compound 4) and 6‐chloroethylureidoethyldiquino[3,2‐b;2′;3′‐e][1,4]thiazine (compound 5) in the amelioration of inflammatory symptoms of imiquimod‐induced psoriasis in mice was investigated. Clobederm®, containing clobetasol propioniate, served as a reference drug. The application of the compounds led to thinning of the epidermis and reduction of the cell layers. The suppressive actions of the compounds were even stronger with regard to pathological changes of the dermis. The compounds also exerted generalized, anti‐inflammatory effects by decreasing the number of circulating leukocytes, lowering subiliac lymph node weight and partially normalizing an altered blood cell composition. The changes in the composition of main cell types in the epidermis and dermis were less affected by the compounds. In addition, both compounds inhibited to a similar degree production of tumor necrosis factor &agr; (TNF &agr;) in human whole blood cell culture. Whereas compound 5 strongly inhibited IL‐8 and CXCL10 chemokines in human keratinocytes – KERTr cell line, transfected with poly(I:C), the suppressive action of compound 4 in this model was weak. In addition, compound 5, but not compound 4, exhibited at low doses proapoptotic properties with regard to colonic cell lines. In summary, we demonstrated the therapeutic potential of two selected azaphenotiazines in the amelioration of the skin pathology elicited in a mouse experimental model of psoriasis. HIGHLIGHTSTopical azaphenothiazines inhibit pathological skin changes in psoriatic mice.Azaphenothiazines suppress generalized cellular changes in lymphoid organs and circulating blood of psoriatic mice.Azaphenothiazines do not show side‐effects in psoriatic mice in contrast to the reference drug Clobederm®.Azaphenothiazines inhibit production of chemokines by a keratinocyte cell line.