RESUMO
The aim of the study was to characterize a series of isoxazole derivatives in several immunological tests in vitro and in vivo, in mouse and human models. The human model included measurement of: viability of peripheral blood mononuclear cells (PBMC), phytohemagglutinin A (PHA)-induced proliferation of PBMC, production of tumor necrosis factor a (TNF a) in whole blood cultures stimulated with lipopolysaccharide (LPS) and growth of SW-948 and L1210 tumor cell lines. Experiments in mice encompassed the following tests: secondary, humoral immune response splenocytes to sheep erythrocytes (SRBC) in vitiv, delayed type hypersensitivity (DTH) to ovalbumin (OVA) and carrageenan-induced foot edema. All compounds were non-toxic against PMBC and displayed differential, dose-dependent suppressive properties in the model of PHA- induced PMBC proliferation. They also exhibited differential, mostly inhibitory effects on TNF a production. The inhibitory actions on growth of tumor cell lines were moderate. M05 (5-amino-3-methyl-N-(4-methyl-benzyl)-4-isoxazolecarboxamide) was most suppressive in the proliferation and TNF a production tests, it was, therefore, selected for in vitro and in vivo studies in the mouse models. The compound inhibited the humoral immune response in vitro, stimulated the inductive phase of DTH in vivo, although it inhibited the eliciting phase of that response. The compound also inhibited the carrageenan skin reaction. M05 combines strong anti-proliferative and anti-inflammatory activities, it is therefore attractive for further studies in more advanced animal models as a potential therapeutic.