Title compounds were tested for their ability to affect the proliferative response of mouse splenocytes to concanavalin A (Con A) and the secondary, humoral immune response of splenocytes to sheep red blood cells (SRBC), measured as the number of antibody-forming cells (AFC). Cyclosporin A (Cs A) served as a reference compound. The compounds demonstrated differential activities in the proliferation test. Some of them were universal stimulators (M5, M6, M9) in all the studied models. Other compounds were regulatory (M2, M3, M4, M7, M8), since they stimulated to various degree the proliferative response of cells at 1-10 mg/ml, whereas the proliferation at high (100mg/ml) concentration was inhibited. Among the stimulators, compounds M1 and M6 deserve special attention, since they strongly stimulated the proliferative response at 100ug/ml (by 4-and 3-fold, respectively). On the other hand, in the humoral immune response in vitro all the compounds exhibited more or less uniform dose-dependent suppressive properties, M2, M5 and M8 being the most potent. Structure-activity relationship of the investigated compounds is discussed. The results of compound M1 on the spontaneous proliferative response of splenocytes and mitogen-induced splenocyte proliferation were described [1].

These studies were supported by the Wrocław Medical University, grant 1312.

Reference:

[1] Marcin Mączyński, Michał Zimecki, Stanisław Ryng, Structure and immunological activity of disubstituted thiosemicarbazide isoxazole derivative, Acta Pol. Pharm., 2004, Vol.61, 82-83.

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