Design, synthesis, and biological evaluation of chalcone oxime derivatives as potential immunosuppressive agents.

A series of new chalcone oximes were synthesized and evaluated for their cytotoxicities and immunosuppressive activities. Chalcone oximes 25 and 27 exhibited lower cytotoxicities and higher inhibitory activities on anti-CD3/anti-CD28 co-stimulated lymph node cell than other compounds. Compound 27 displayed 200-fold lower cytotoxicity and potent inhibition activity (SI=176.69) close to cyclosporin A (SI=154.13). The preliminary mechanism of inhibition effect of compounds 25 and 27 was also detected by flow cytometry, and the compounds exerted immunosuppressive activities via inducing the apoptosis of activated lymph node cells in a dose dependent manner. The deep mechanism of apoptosis was detected by Western blot analysis.