In our studies we showed that a new isoxazolotriazepine derivatives (I) [1], in the biological studies have immunosuppressive and antiinflammatory activities, in the mouse model. The compounds inhibited both the humoral and cellular immune response and was effective not only upon ip administration but also when given orally, indicating good bioaccessibility and a potential therapeutic application. Other studies revealed the lack of toxicity of the compound even at very high doses.

Although immunosuppressory isoxazoles, such as leflunomide, express anti-inflammatory properties and are sometimes used in combination with other immunosuppressors like Cyclosporine A (CsA), their mechanism of action differs from that of CsA. In particular, the mitogen-induced T cell proliferation is not affected.That was also a case with regard to I which stimulated rather than inhibited phytohemagglutinin-induced proliferation of human mononuclear blood cells, in addition, the compound did not affect IL-10 production, in contrast to CsA. Another isoxazole II, [2] also stimulated mitogen-induced T cell proliferation, and strongly stimulated both humoral and cellular immune response in mice.

Interesting, the structure II is very closely related to that of I, differing only in substitution of one group in the isoxazolo[5,4-e]triazepine ring. Therefore, within the family of isoxazoles, both immunosuppressive and immunostimulatory compounds may be found. It is also clear that immunostimulatory activity in some tests i.e. mitogen-induced cell proliferation does not exclude anti-inflammatory activity of a given compounds as in the case of I.

References:

[1]. St. Ryng, M. Zimecki: „Pochodne izoksazolotriazepinonów oraz sposób ich wytwarzania” Polish Patent Application 193939 (25-10-2006).

[2]. St. Ryng, M. Zimecki: „Pochodna izoksazolotriazepinonu oraz sposób jej wytwarzania”

Polish Patent Application 193279 (18-08-2006).

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