Selected azaphenothiazines inhibit delayed type hypersensitivity and carrageenan reaction in mice

Several, previously selected azaphenothiazines, as strongly antiproliferative agents in in vitro models, were subjected to evaluation for their potential immunosuppressive effects in the model of delayed type hypersensitivity (DTH) to ovalbumin (OVA) in BALB/c mice and in foot pad inflammation induced by carrageenan in CBA mice. In the DTH model the compounds were given to mice intraperitoneally (i.p.) in 50μg or 250μg doses, 1h before the elicitation of the response. In the carrageenan-induced foot pad inflammation the compounds were given i.p. in 50μg or 250μg doses, 24h and 2h before administration of carrageenan. Among the compounds, the significantly suppressive activities in both models were exhibited only by compound 5 (6-chloroethylureidoethyldiquino[3,2-b;2',3'-e][1,4]thiazine) and compound 4 (6-acetylaminobutyl-9-chloroquino[3,2-b]benzo[1,4]thiazine). Structure-activity relationship, plausible mechanism of action and potential application in therapy of the compounds are discussed.